Annual Review 2004

ANNUAL REVIEW 2004

The Wellcome Trust is an independent research-funding charity, established under the will of Sir Henry Wellcome in 1936. It is funded from a private endowment, which is managed with long-term stability and growth in mind.

Its mission is to foster and promote research with the aim of improving human and animal health. Its work covers four areas:

Knowledge – improving our understanding of human and animal biology in health and disease, and of the past and present role of medicine in society.

Resources – providing exceptional researchers with the infrastructural and career support they need to fulfil their potential.

Translation – ensuring maximum health benefits are gained from biomedical research.

Public engagement – raising awareness of the medical, ethical and social implications of biomedical science. www.wellcome.ac.uk CONTENTS 1 THE WELLCOME TRUST An independent, privately owned endowed medical research charity. Our mission is to foster and promote research with the aim of improving human and animal health.

CONTENTS AIMS AND OBJECTIVES BOARD OF GOVERNORS EXECUTIVE BOARD 2 Director’s statement Our four Aims identify the priorities 20 Translation Sir Dominic Cadbury Dr Mark Walport on which we concentrate. Each Advancing the translation Chairman Director of the Wellcome Trust Aim is underpinned by a series of Trust-funded research into health benefits. 4 Knowledge of Objectives which establish Professor Martin Bobrow Linda Arter 14 Resources the practical measures being taken • Promoting patient-orientated Deputy Chairman Director of Finance to achieve the Aims and, ultimately, and health services research. and Information Management 20 Translation our mission. Professor Adrian Bird • Advancing the dissemination 28 Public engagement Dr Ted Bianco 4 Knowledge and exploitation of the results Professor Christopher Edwards Director of Technology Transfer of Trust-funded research. Advancing knowledge and 34 A year at the Wellcome Trust understanding in the biomedical 28 Public engagement Alastair Ross Goobey John Cooper 36 Financial summary sciences and their impact on Engaging with the public Director of Human Resources 37 The funding year society – past, present and future. through informed dialogue. Dame Patricia Hodgson and Services 38 Immunology and Infectious Disease • Stimulating an informed • Supporting basic, applied dialogue to raise awareness Professor Ronald Plasterk Dr David Lynn 40 Molecules, Genes and Cells and strategically important and understanding of biomedical Head of Strategic Planning and Policy 42 Neuroscience and Mental Health research in biomedical sciences. science, its achievements, Professor Peter Smith Clare Matterson 43 Physiological Sciences applications and implications. • Researching the societal Professor Dame Jean Thomas Director of Medicine, Society 44 Populations and Public Health impact of biomedical science – and History 45 Medical Humanities past, present and future. Edward Walker-Arnott 46 Technology Transfer David Phillipps 14 Resources Director Designate of Finance 47 Wellcome Trust Genome Campus Contributing to a long-term and vibrant research environment. 48 Public Engagement Dr Sohaila Rastan 50 Funding committees • Human resources: meeting Director of Science Funding training and career development needs of researchers. John Stewart Head of Legal and Company Secretary This Annual Review covers the Wellcome • Physical resources: building Trust’s financial year 1 October 2003 to suitable conditions for research. 30 September 2004. As at January 2005

L to R The bacterium, A portrait of twins Escherichia coli. by David Teplica. Kenyan child. Interactive exhibit Human embryo at the science centre, at the blastocyst stage. Thinktank, in Birmingham. CONTENTS 1 THE WELLCOME TRUST An independent, privately owned endowed medical research charity. Our mission is to foster and promote research with the aim of improving human and animal health.

L to R The bacterium, A portrait of twins Escherichia coli. by David Teplica. Kenyan child. Interactive exhibit Human embryo at the science centre, at the blastocyst stage. Thinktank, in Birmingham. DIRECTOR’S STATEMENT DIRECTOR’S STATEMENT 2 3 WORKING WITH OTHERS It’s been a year when working in partnership has delivered real benefits.

Highlights of the year • A biochemical defect causing • Avian flu victims are treated • A trial with steroids markedly neonatal diabetes is identified, at Wellcome-funded facilities cuts deaths from tuberculous • The highly accurate and complete allowing babies to be given in Vietnam, capturing valuable meningitis in Vietnam. ‘gold standard’ human genome medication rather than injections. data on the impact of the virus. sequence is released. • ‘Myskin’, an innovative dressing • Beneficial effects of rapamycin • Analysis of clinical trials data incorporating patients’ own cells, • Mutations in the ERBB2 gene analogues in models of for artemisinin combination is launched in the UK NHS. are discovered in a subset of lung Huntington’s disease suggest therapy confirms its potency cancers, opening up the prospect a new therapeutic approach. as an antimalarial drug. • Pain exhibition at the Science of targeted therapy. Museum attracts a record number of visitors.

Looking back on a busy year, I am City, which I had the honour of accepting enables us – and, indeed, requires us – funders, including the Department for This year has seen many exciting of our desire to engage with our delighted at the progress we have seen for the Trust during a fascinating visit to play an important role as a critic of International Development, how we research findings published. A small multitude of stakeholder communities. – the discoveries our researchers have to see the work of our researchers Government when it pursues policies might best work together. Moreover, selection of these are summarised Our new corporate identity similarly made, the accelerating application in Thailand, Vietnam and Laos. Professor that may have an adverse impact on with the UK assuming presidency of the in the following pages. It is clear we reflects a desire to be seen as of research, and the changes we have White and Dr Jeremy Farrar were also biomedical research for public good. G8 group of nations on 1 January 2005, are living in a golden age of biomedical approachable, as well as distinctive made within the Wellcome Trust itself. honoured by the Committee. This We have worked very hard during the and a spotlight on Africa as a major research, as human genome data and and independently minded. And I am also pleased that so much recognition is an endorsement of our year to gain acceptance of amendments priority, we have a real opportunity high-throughput technologies offer has been achieved in partnership with long-standing collaborative approach of proposed legislation that could to make a difference to a continent that experimental possibilities undreamed All these strands will come together in others. I firmly believe that scientific in the region. have serious adverse consequences suffers so badly from disease. of a generation ago; similarly, new our new strategic plan, which we will opportunities will be exploited to best for important medical research. approaches to imaging and the study develop during 2005 and launch towards effect, and medical needs met, when UK science In our Public Engagement work, we of the brain give us unprecedented the end of the year. The strategic plan, people work together to harness their In the UK we have continued to work Partnership also increases the developed ground-breaking exhibitions insight into the workings of the brain. the follow-up to Planning for the Future: energies to common purpose. constructively with the UK Government, effectiveness of our voice in this public with the Science Museum and the British The Wellcome Trust 2000–2005, will which has consistently recognised the policy work; we have worked closely with Museum (and in 2005 will be collaborating An important challenge is not only outline our aims for 2005–2010, and Our Major Overseas Research importance of the country’s research the UK research funding and academic with the Victoria and Albert Museum to nurture this age of discovery but also identify more specifically how we will Programmes in developing countries, base. There is an outstanding community community to produce joint responses on a new exhibition on touch). Our to ensure that we capture practical achieve these. for example, have been based on of imaginative and productive researchers to, among other things, the draft Human science centre and museum exhibit medical benefits afforded by the flow partnerships with local Governments in the UK. We will continue to support Tissue Bill and Mental Capacity Bill. renewal initiative, Rediscover, was also a of new knowledge. Ultimately, it is the unstinting work and academic and health infrastructures. research in the UK whilst its excellent A single coherent voice has undoubtedly partnership venture – with the Millennium of our grantholders that enables us By dealing with local issues, they have science base is maintained. The additional benefited all parties and led to more Commission and the Wolfson Foundation. Streams to meet our objectives, and we look provided genuine benefits to their host funds for science provided in the 2004 considered legislation. Internally, our year was marked forward to continuing to work in countries. Because of these strong links, Spending Review, including more Building work began in the year for by a move into a new building, the partnership with them to advance their activities have quickly fed into local resources as an explicit underpinning Two of the most important and the National Science Learning Centre, implementation of a new corporate towards our ultimate goal – improving policy and practice. of charity-funded research, are signals challenging areas are clinical and funded by us as part of a £51 million identity, and the introduction human and animal health. that the Government is as committed international research. The creation partnership with the Department for of our streams model of funding. This year we report on the continuing as we are to the future of UK science. of a new partnership, the UK Clinical Education and Skills. The Science Mark Walport success of artemisinin combination Research Collaboration (UKCRC), Learning Centre network will provide Our new building has been designed Director therapy for malaria, pioneered by There are other areas in which we are is recognition that clinical research a major boost to science teaching to encourage greater interaction between January 2005 Professor Nick White and colleagues working closely with the Government. will only thrive if all the key protagonists in the UK, benefiting the next generation staff – fostering ‘internal partnerships’ in South-east Asia, as well as a trial A long-standing partnership, to construct work together – funders, the health of scientists and, more generally, and a greater sense of integration and of steroid therapy in tuberculous the UK’s new synchrotron facility, received service and the higher education helping to create a scientifically common purpose. Our building is also meningitis, which has significantly a further financial boost this year (£120 community. We look forward to enquiring population. open and welcoming, a physical symbol cut death rates, and has led to changes million in total, with more than £100 announcing new initiatives under the in government health policy. million extra from the Government). UKCRC umbrella in the very near future.

Recently, the Wellcome Trust was Although we are pleased to work in We have also developed a joint awarded a Merit Award from the partnership with Government in support commitment to prioritise malaria People’s Committee of Ho Chi Minh of research, our independence also research, and are discussing with other Mark Walport (right) visiting a ward at Mahosot Hospital, Laos. DIRECTOR’S STATEMENT DIRECTOR’S STATEMENT 2 3 WORKING WITH OTHERS It’s been a year when working in partnership has delivered real benefits.

Supporting basic, applied and strategically important research in biomedical sciences. Researching the societal impact of biomedical science – past, present and future. KNOWLEDGE

The human genome sequence is a are being gained into the brain’s • Page 10: A new twist to the spread driving force behind much of today’s control of our behaviour: of the Leishmania parasite; biomedical research. In particular, • Page 11: Intercontinental spread research is focusing on the impact • Page 8: A possible cause of drug-resistant malaria; of genetic differences between of inflexible thinking patterns; • Page 11: How weather systems people, many of which affect health. • Page 8: What happens in the brain affect population density modelling. Another key theme is how genetic when we think we are being lied to; information is translated into • Page 9: The ethically sensitive area Finally, we are gaining new insight biological function: of mental capacity and informed into type 2 diabetes – which is leading consent. to better treatments for this growing • Page 6: Surprises in the ‘finished’ health problem: human genome sequence; On a different scale, infectious • Page 6: The impact of genetic organisms continue to threaten our • Page 12: How an ion channel population structure in the UK; health. A key issue is to understand mutation leads to diabetes in babies; • Page 7: How an unusual genetic how such diseases are spread, • Page 12: Type 2 diabetes caused quirk causes a deadly and the impact the environment by a single gene defect; inherited disease. has on their transmission: • Page 13: Possible targeted treatments for different forms Neuroscience is a second area of • Page 10: Is global warming the cause of diabetes. great progress. Fascinating insights of the resurgence of malaria in Africa? KNOWLEDGE KNOWLEDGE 4 5

Supporting basic, applied and strategically important research in biomedical sciences. Researching the societal impact of biomedical science – past, present and future. KNOWLEDGE

The International Human Genome protein-coding genes in the genome, Finding that a particular genetic variant Life would be much easier if we Dyskeratosis congenita is a is faulty, and telomeres erode at an Sequencing Consortium has published far fewer than the 100 000 confidently is more common in people with, say, understood the genetic structure devastating disease that leads accelerated rate. Tissues with actively its scientific description of the finished predicted a decade ago, and even diabetes than in those without is a clue of the UK – and that is the goal to premature ageing, bone marrow proliferating cells – gut, skin and bone human genome sequence – the ‘gold the 30–40 000 estimated in 2001. that the gene may be increasing of a new £2.3 million Wellcome- failure and cancer. Over the past marrow – are the first to be affected. standard’ genome. susceptibility to the disease. But is funded project being led by Sir Walter few years, Professor Inderjeet Dokal The earliest sign of accelerated wear A further intriguing finding is the number the association real, or are the different Bodmer, with Professor Donnelly and colleagues at Imperial College, and tear is usually abnormal skin The current genome sequence of pseudogenes – genes that have genetic make-ups of the people and Professor Lon Cardon in Oxford. London, have identified the genetic pigmentation followed, years later, contains 2.85 billion nucleotides and lost their function and are gradually involved in the study – the population DNA will be collected from 3500 basis of this rare inherited disorder. by cancer, premature ageing and bone encompasses around 99 per cent of the decaying away. Indeed, recent studies structure – clouding the results? people, in 30 rural locations, whose Most recently, they have clarified marrow failure, which often proves fatal. euchromatic (or gene-containing) portion have already identified about 20 000 parents and grandparents also lived one of its most perplexing features – of the human genome. All but 341 of pseudogenes, and there may even The extent of the problem was in the same area. why symptoms appear earlier But why do children’s symptoms the 150 000 gaps present in the 2001 be more ‘dead’ genes in our genome highlighted in a study by Professor in successive generations.1 appear at an earlier age than in their working draft sequence have been than ‘live’ ones. Peter Donnelly and colleagues in Oxford The data and DNA samples will become parents? This phenomenon is also filled in, and the sequence is 99.99 and Montreal, which examined 15 000 a national resource for researchers Affecting one person per million, seen in some other genetic disorders, per cent accurate – ten times more The largest single contribution to the DNA variations across three population to use to match their disease samples, the mutations that cause dyskeratosis where a three-letter fragment of DNA accurate than the original goal. human genome sequence was made groups (European American, African thus reducing the chances of spurious congenita disrupt telomeres – the tips multiplies in successive generations. by the Wellcome Trust Sanger Institute. American and Asian) and within the associations. The resource will be of chromosomes. When chromosomes What Professor Dokal and colleagues The most surprising finding – and one It is now trying to work out how so few Asian group.1 Using statistical models, particularly valuable with a number are copied during cell division, telomeres discovered was that the length that hit the headlines worldwide – was genes can build something as complex they found that the effects of population of very large population studies, tend to get shorter. To compensate of a patient’s telomeres predicted the tiny number of protein-coding as a human being. structure increase markedly with sample such as the UK Biobank project, for this, actively dividing cells make when symptoms would first emerge – genes in the genome. The new analysis size, leading to false positive results now underway. an enzyme, telomerase, which repairs the shorter the telomere, the sooner predicts that there are only 20–25 000 and missed real effects. telomeres. Without it, cells tend symptoms appeared. As the telomeres 1 Marchini J, Cardon LR, Phillips MS, to go through a certain number get shorter in successive generations, Donnelly P. The effects of human population This is a real headache for researchers structure on large genetic association studies. of divisions and then die. so the disease strikes earlier. searching for genetic factors that have Nat Genet 2004; 36(5): 512–7 only small effects on common diseases, In dyskeratosis congenita, mutant genes 1 Vulliamy T et al. Disease anticipation is associated with progressive telomere shortening in families who need to examine large numbers (such as that coding for telomerase, with dyskeratosis congenita due to mutations of people. TERC) mean that chromosome repair in TERC. Nat Genet 2004; 36(5): 447–9.

L to R Sequencing at the Professor Inderjeet Wellcome Trust Dokal (left) of Imperial Sanger Institute. College London. Professor Lon Cardon, Faulty chromosome who is studying genetic repair is the cause of variation in the dyskeratosis congenita. UK population. KNOWLEDGE KNOWLEDGE 6 7 VANISHING GENES GENE SHORT NOT SWEET GEOGRAPHY The ‘gold standard’ genome has been published DNA variation shows geographical The length of telomeres can predict when a rare inherited and is full of surprises. clustering, which can distort the disorder will strike. findings from large genetic studies.

Serotonin depletion could explain the inflexible behaviours Brain imaging is revealing brain Patients should consent to medical treatment. But an inability to give seen in people with psychiatric disorders. activity during social interactions. reasoned consent may be more common than doctors appreciate.

People with obsessive–compulsive To explore the possible involvement Humans are intensely social creatures. specific areas of the brain lit up when To consent to medical treatment, interviewed inpatients, they rated just disorder (OCD) or schizophrenia, of serotonin pathways, the Cambridge It is vital, then, that our brains can people thought they were being patients should be making voluntary 8 per cent as lacking mental capacity.1 and those who abuse drugs, team depleted serotonin from the perceive and interpret socially relevant deceived.2 These areas are linked and informed choices, and have the typically have something in common: orbito-frontal cortex of marmosets. information. A team led by Professor to emotional responses, which fits mental capacity to make a decision. Most patients probably rely on doctors inflexible behaviours. New research They then tested the animals’ ability Chris Frith at the Institute of Neurology with the fact that we find deception Patients lack mental capacity when to make the most appropriate decision points the finger at deficiencies to solve both a visual learning task in London has been locating the neural emotionally distressing. they cannot understand the for them. A need to assess mental in the neurotransmitter serotonin: and a ‘reverse learning’ task. areas we engage during a range information being given to them, capacity in a medically pressing situation as Professor Trevor Robbins, of social interactions. Empathy is a unique human attribute, or use it to decide on a course of could present significant difficulties Dr Angela Roberts and colleagues Those marmosets whose serotonin had a ‘social glue’ that allows us to action, or are unable to communicate to the medical profession. On the other at the University of Cambridge have been depleted were stuck in a learning One valuable skill is our ability to understand what others feel. To explore their decision. Usually, mental hand, there is clearly also a need to discovered, depletion of serotonin rut: they had no difficulty in acquiring associate people with particular values the neural basis of empathy, Professor capacity is taken as read unless the protect vulnerable patients, particularly in the prefrontal cortex leads knowledge, but made more mistakes or characteristics: are they honest, Frith’s group compared brain activity patient’s difficulties are very obvious. when major – and irreversible – medical to very similar abnormalities.1 in ‘unlearning’, suggesting that their trustworthy and so on. To understand in volunteers either receiving a painful However, recent research suggests decisions are being made. cognitive flexibility had declined. how the brain responds to people’s stimulus or witnessing their loved ones that the numbers of mentally We need cognitive flexibility to cope A similar effect has been seen in human moral standing, volunteers were experience pain. incapacitated patients may be These kinds of issues are being with daily life. Both learning and volunteers whose serotonin levels were scanned while they judged faces being significantly underestimated. considered in the UK’s draft Mental ‘unlearning’ – changing tack in light reduced by dietary manipulation. of people known to be fair or unfair Painful stimuli triggered both physical Capacity Bill. The researchers suggest of further experience – are critical players in the Prisoner’s Dilemma game. and emotional areas of the brain, Professor Matthew Hotopf and that, even if legislation is seen as too to human experience. If that flexibility The finding that low serotonin in The faces of fair players lit up specific but witnessing someone else in pain colleagues at the Institute of Psychiatry, heavy handed, the issue of patients’ breaks down, a whole array of the prefrontal cortex inhibits flexible neural circuits, confirming that there triggered just the emotional response.3 Preston and Yale tested the degree mental capacity should be given more uncontrollable behaviours can emerge: thinking provides insight into human is an area in the brain dedicated So we cannot share a loved one’s of cognitive impairment of patients attention by doctors. toe tapping, finger drumming, tics, psychiatric disorders. Not only will it to processing information about physical pain, but we can share admitted to a London hospital. knocking or pacing. In humans, there help clinicians understand the difficulties people’s moral status.1 a similar emotional experience. Some 31 per cent of inpatients were 1 Raymont V et al. Prevalence of mental incapacity in medical inpatients and associated are other signs that the brain has lost experienced by patients with OCD, considered to lack mental capacity. risk factors: cross-sectional study. Lancet 2004; its flexibility: a rigid way of looking at schizophrenia or drug-induced It is also useful to know whether a 1 Singer T et al. Brain responses to the acquired However, when clinical teams 364(9443): 1421–7. moral status of faces. Neuron 2004; 41(4): things, a refusal to let go of an idea, damage, but it also has significant person is trying to deceive us. Working 653–62. or fanatical attitudes. implications for their treatment. with collaborators in France, Professor 2 Grezes J, Frith C, Passingham RE. Brain Frith studied people who had been mechanisms for inferring deceit in the actions of others. J Neurosci 2004; 24(24): 1 Clarke H et al. Cognitive inflexibility following watching videos of actors lifting prefrontal serotonin depletion. Science 2004; 5500–5. 304: 878–80. a box. The participants were asked 3 Singer T et al. Empathy for pain involves to judge whether the actors were lifting the affective but not sensory components a heavy box or just pretending. Again, of pain. Science 2004; 303(5661): 1157–62.

L to R Neurons in the brain. Professor Chris Frith Brain imaging can reveal of the Institute the neural areas used of Neurology, London. during social interactions. People with Alzheimer’s disease may lack the mental capacity to give informed consent. KNOWLEDGE KNOWLEDGE 10 11 HEATED VOMITING SAND FLIES UNWANTED SHEEP DIP DISCUSSION IMPORT Global warming does not appear By creating a sticky ‘hairball’ in the sand fly gut, the Leishmania Scientists have tracked down In a study of periodic sheep decimations, seasonal fluctuations to have driven the rise in malaria parasite promotes its transmission – and ensures its survival the origins of Africa’s drug- in bad weather may be better at predicting mortality than local climate. across Africa. in its new host. resistant malaria parasites.

A belief that global warming is A bite from an infected sand fly is all secretion that forms a thick plug Scientists co-funded by the Wellcome Our lives and those of other species failed to predict these deaths. Instead, responsible for the recent resurgence it takes to catch the tropical disease in the sand fly’s gut. This ‘hairball’ Trust and the US National Institutes are inextricably entwined – we are variation in a large-scale, seasonal of malaria is misguided, according leishmaniasis. Yet exactly how the stops the fly from feeding properly of Health have uncovered evidence all part of a natural system. Climate climate index spanning several months – to an analysis of 80 years of climate sand fly delivers its lethal cargo has, and, as a result, the insect bites that drug-resistant malaria in Africa obviously has an enormous impact the North Atlantic Oscillation – provided data in Africa. The analysis, led by until recently, remained a mystery. repeatedly, and for longer, increasing was imported from South-east Asia. on this system, yet the links between the most reliable forecast. Dr Simon Hay and colleagues at Now Wellcome-funded scientists the likelihood of transmission.1 climate and population numbers the University of Oxford, found no have discovered a key aspect of The boom in air travel has meant that are rarely well understood. With A harsh spell – heavy rain, strong winds evidence that climate had changed transmission: a sticky gel secreted As well as manipulating the behaviour malaria travels the globe too. Every year current fears about climate instability, or low temperatures – at any time during the suitability for malaria transmission by the parasite and regurgitated by of its insect vector, the parasite 30 000 malaria cases are imported into this is becoming a matter of a three-month period was associated across Africa.1 the sand fly. secretion also affects its new human industrialised countries. The figure for growing concern. with high sheep mortality, either host. It includes a long, sugar-coated, Africa is unknown, but is likely to immediately or after a few days. After decades in decline, malaria Leishmaniasis is a parasitic disease phosphorylated protein (filamentous be substantial. A team of scientists led by Dr Bryan This appears to be obscured in the local has made a comeback in many parts affecting about 12 million people proteophosphoglycan, fPPG), which Grenfell at the University of Cambridge climate data, but is captured in crude of Africa. Malaria mortality in young worldwide, causing disfiguring ulcers is regurgitated by the sand fly and Today pyrimethamine (coformulated with has spent 20 years exploring the form by the North Atlantic Oscillation.1 children almost doubled from the and, in severe cases, death. Major injected into the victim. The fPPG sulphadoxine) is a mainstay of malaria impact of climatic factors on a natural 1980s to the 1990s. The disease now epidemics have occurred in India appears to promote parasite survival treatment. But mutations in a gene population – Soay sheep living on These counter-intuitive results suggest causes around 3000 deaths each day. and Bangladesh, and it is a scourge and exacerbates disease. known as dhfr (dihydrofolate reductase) a remote Scottish island. This sheep that, in order to predict population of migrating populations, such as those allow the parasite to survive. Parasites population ‘crashes’ every three to four changes in response to ecological To find out whether this resurgence affected by civil war. The research has important implications. have up to four mutations in the dhfr years, when 70 per cent of the animals stresses such as climate change, could be linked to climate, Dr Hay’s It immediately suggests possible new gene – the more they have, the hardier perish during winter. They typically die large-scale, seasonal climate indices team used a climate-driven biological Infection starts when a sand fly bite strategies for tackling transmission, they are; with the full complement of from starvation, either because they spanning several months – such as model of malaria transmission to show injects the single-celled parasite by blocking the action of the gel. But it four, they are resistant to all drugs burn up more energy to keep warm the North Atlantic Oscillation – may that changing patterns of temperature Leishmania, along with sand fly saliva. also highlights how interactions between targeting this enzyme. or because there is little grass left be preferable to local records. In the and rainfall between 1911 and 1995 However, a team led by Dr Paul Bates all the key players – parasite, vector and to graze on. longer term, though, the need is to had not made for a more hospitable at the Liverpool School of Tropical host – need to be studied to give a clear By genotyping the dhfr gene and identify more specifically which local climate for mosquitoes and malaria. Medicine has discovered that view of disease transmission. surrounding DNA, Dr Cally Roper, Dr Grenfell’s team has been trying factors are ecologically most important. In a couple of regions, shifts in malaria Leishmania is not a passive passenger London School of Hygiene and Tropical to find out why this population is so transmission suitability were linked in this process. It produces a gelatinous 1 Rogers ME et al. Transmission of cutaneous Medicine, and collaborators have shown unstable. They looked for correlations 1 Hallett TB et al. Why large-scale climate indices leishmaniasis by sand flies is enhanced by seem to predict ecological processes better to changes in rainfall. regurgitation of fPPG. Nature 2004; 430: 463–7. that the most resistant parasites in Africa with a range of possible causes and than local weather. Nature 2004; 430: 71–5. did not arise there, but originated in found that foul weather over a three- Data collection has been funded by the Wellcome Rather than global trends, the South-east Asia.1 The parasite with four month period was the strongest Trust, the Natural Environment Research Council and the Biotechnology and Biological Sciences researchers emphasise that local mutations has not yet been seen predictor of a population crash. Research Council. factors – migration, health service in Africa, but if malaria parasites are Surprisingly, local weather variables provision and, particularly, the rise L to R travelling from Asia to Africa, then there in drug resistance – are likely to have Climate is unlikely to play Boy with an ulcer caused is every chance it could be imported a part in the malaria by Leishmania infection. a bigger impact on malaria transmission. resurgence in Africa. Malaria-infected and become established. Sand flies regurgitate red blood cells. 1 Small J, Goetz SJ, Hay SI. Climatic suitability a sticky gel secreted Soay sheep populations 1 Roper C et al. Intercontinental spread for malaria transmission in Africa, 1911–1995. by the Leishmania on a remote Scottish of pyrimethamine-resistant malaria. Science Proc Natl Acad Sci USA 2003; 100(26): 15341–5. parasite which makes island are sensitive 2004; 305(5687): 1124. infection more likely. to weather conditions. KNOWLEDGE KNOWLEDGE 10 11 HEATED VOMITING SAND FLIES UNWANTED SHEEP DIP DISCUSSION IMPORT Global warming does not appear By creating a sticky ‘hairball’ in the sand fly gut, the Leishmania Scientists have tracked down In a study of periodic sheep decimations, seasonal fluctuations to have driven the rise in malaria parasite promotes its transmission – and ensures its survival the origins of Africa’s drug- in bad weather may be better at predicting mortality than local climate. across Africa. in its new host. resistant malaria parasites.

A belief that global warming is A bite from an infected sand fly is all secretion that forms a thick plug Scientists co-funded by the Wellcome Our lives and those of other species failed to predict these deaths. Instead, responsible for the recent resurgence it takes to catch the tropical disease in the sand fly’s gut. This ‘hairball’ Trust and the US National Institutes are inextricably entwined – we are variation in a large-scale, seasonal of malaria is misguided, according leishmaniasis. Yet exactly how the stops the fly from feeding properly of Health have uncovered evidence all part of a natural system. Climate climate index spanning several months – to an analysis of 80 years of climate sand fly delivers its lethal cargo has, and, as a result, the insect bites that drug-resistant malaria in Africa obviously has an enormous impact the North Atlantic Oscillation – provided data in Africa. The analysis, led by until recently, remained a mystery. repeatedly, and for longer, increasing was imported from South-east Asia. on this system, yet the links between the most reliable forecast. Dr Simon Hay and colleagues at Now Wellcome-funded scientists the likelihood of transmission.1 climate and population numbers the University of Oxford, found no have discovered a key aspect of The boom in air travel has meant that are rarely well understood. With A harsh spell – heavy rain, strong winds evidence that climate had changed transmission: a sticky gel secreted As well as manipulating the behaviour malaria travels the globe too. Every year current fears about climate instability, or low temperatures – at any time during the suitability for malaria transmission by the parasite and regurgitated by of its insect vector, the parasite 30 000 malaria cases are imported into this is becoming a matter of a three-month period was associated across Africa.1 the sand fly. secretion also affects its new human industrialised countries. The figure for growing concern. with high sheep mortality, either host. It includes a long, sugar-coated, Africa is unknown, but is likely to immediately or after a few days. After decades in decline, malaria Leishmaniasis is a parasitic disease phosphorylated protein (filamentous be substantial. A team of scientists led by Dr Bryan This appears to be obscured in the local has made a comeback in many parts affecting about 12 million people proteophosphoglycan, fPPG), which Grenfell at the University of Cambridge climate data, but is captured in crude of Africa. Malaria mortality in young worldwide, causing disfiguring ulcers is regurgitated by the sand fly and Today pyrimethamine (coformulated with has spent 20 years exploring the form by the North Atlantic Oscillation.1 children almost doubled from the and, in severe cases, death. Major injected into the victim. The fPPG sulphadoxine) is a mainstay of malaria impact of climatic factors on a natural 1980s to the 1990s. The disease now epidemics have occurred in India appears to promote parasite survival treatment. But mutations in a gene population – Soay sheep living on These counter-intuitive results suggest causes around 3000 deaths each day. and Bangladesh, and it is a scourge and exacerbates disease. known as dhfr (dihydrofolate reductase) a remote Scottish island. This sheep that, in order to predict population of migrating populations, such as those allow the parasite to survive. Parasites population ‘crashes’ every three to four changes in response to ecological To find out whether this resurgence affected by civil war. The research has important implications. have up to four mutations in the dhfr years, when 70 per cent of the animals stresses such as climate change, could be linked to climate, Dr Hay’s It immediately suggests possible new gene – the more they have, the hardier perish during winter. They typically die large-scale, seasonal climate indices team used a climate-driven biological Infection starts when a sand fly bite strategies for tackling transmission, they are; with the full complement of from starvation, either because they spanning several months – such as model of malaria transmission to show injects the single-celled parasite by blocking the action of the gel. But it four, they are resistant to all drugs burn up more energy to keep warm the North Atlantic Oscillation – may that changing patterns of temperature Leishmania, along with sand fly saliva. also highlights how interactions between targeting this enzyme. or because there is little grass left be preferable to local records. In the and rainfall between 1911 and 1995 However, a team led by Dr Paul Bates all the key players – parasite, vector and to graze on. longer term, though, the need is to had not made for a more hospitable at the Liverpool School of Tropical host – need to be studied to give a clear By genotyping the dhfr gene and identify more specifically which local climate for mosquitoes and malaria. Medicine has discovered that view of disease transmission. surrounding DNA, Dr Cally Roper, Dr Grenfell’s team has been trying factors are ecologically most important. In a couple of regions, shifts in malaria Leishmania is not a passive passenger London School of Hygiene and Tropical to find out why this population is so transmission suitability were linked in this process. It produces a gelatinous 1 Rogers ME et al. Transmission of cutaneous Medicine, and collaborators have shown unstable. They looked for correlations 1 Hallett TB et al. Why large-scale climate indices leishmaniasis by sand flies is enhanced by seem to predict ecological processes better to changes in rainfall. regurgitation of fPPG. Nature 2004; 430: 463–7. that the most resistant parasites in Africa with a range of possible causes and than local weather. Nature 2004; 430: 71–5. did not arise there, but originated in found that foul weather over a three- Data collection has been funded by the Wellcome Rather than global trends, the South-east Asia.1 The parasite with four month period was the strongest Trust, the Natural Environment Research Council and the Biotechnology and Biological Sciences researchers emphasise that local mutations has not yet been seen predictor of a population crash. Research Council. factors – migration, health service in Africa, but if malaria parasites are Surprisingly, local weather variables provision and, particularly, the rise L to R travelling from Asia to Africa, then there in drug resistance – are likely to have Climate is unlikely to play Boy with an ulcer caused is every chance it could be imported a part in the malaria by Leishmania infection. a bigger impact on malaria transmission. resurgence in Africa. Malaria-infected and become established. Sand flies regurgitate red blood cells. 1 Small J, Goetz SJ, Hay SI. Climatic suitability a sticky gel secreted Soay sheep populations 1 Roper C et al. Intercontinental spread for malaria transmission in Africa, 1911–1995. by the Leishmania on a remote Scottish of pyrimethamine-resistant malaria. Science Proc Natl Acad Sci USA 2003; 100(26): 15341–5. parasite which makes island are sensitive 2004; 305(5687): 1124. infection more likely. to weather conditions. KNOWLEDGE KNOWLEDGE 12 13 CROSS-CHANNEL DISSECTING TAILORED TREATMENT BALANCING THERAPY DIABETES ACTS Thanks to the discovery of the precise cause of infant diabetes, The mechanisms of type2 Two forms of diabetes respond very differently to drugs – pointing young children can be given medication rather than insulin injections. (adult-onset) diabetes are the way to tailored drug treatments based on genetic make-up. beginning to be unravelled.

With fears of an ‘obesity epidemic’ growing, it is crucial we learn more about the metabolic processes underlying our energy balance, and how they can trigger disease.

in the blood’s glucose levels, and alter on the KATP channel, and some patients metabolism. This study reveals its central drugs and the doses used could then • CBS domains are tandemly repeated their secretion of insulin accordingly. with mutant Kir6.2 did secrete insulin role in cellular responses to insulin.1 Professor Andrew Hattersley, Ewan be refined according to a patient’s 60 amino acid domains found in Crucial to this process is an ion channel when given such drugs. Follow-up Pearson and colleagues at the genetic background. most living organisms. Although – the ATP-sensitive potassium channel studies have confirmed that children with Mutations in AKT2 are unlikely to explain Peninsula Medical School, Exeter, mutations in CBS gene sequences 1 Pearson ER et al. Genetic cause (KATP channel) – that spans the Kir6.2 mutations no longer need insulin most cases of diabetes. A more likely compared the drug responses of people cause a range of inherited diseases, of hyperglycaemia and response to treatment membrane of beta cells. injections when given sulfonylurea drugs. scenario is that other subtle variations with a specific form of diabetes caused in diabetes. Lancet 2003; 362: 1275–81. the domain’s role has been unclear. in or around the AKT2 gene contribute by mutations in the HNF-1α gene with Professor Grahame Hardie and If glucose levels go up, more ATP 1 Gloyn AL et al. Activating mutations in the gene to the common form of diabetes. those in other patients who had colleagues at Dundee have now encoding the ATP-sensitive potassium-channel is made in the cell; this ATP binds subunit Kir6.2 and permanent neonatal diabetes. The team is now hunting for variants diabetes of unknown cause. shown that the domains bind to the channel and closes it, thereby N Engl J Med 2004; 350: 1838–49. in populations with type 2 diabetes adenosyl compounds (such as AMP, to explore this possibility. ATP or S-adenosyl methionine). In many cases, including AMPK, a key 1 George S et al. A family with severe insulin energy sensor in the body, the resistance and diabetes due to a mutation in AKT2. Science 2004; 304: 1325–8. domains appear to link the protein’s activity to the cell’s energy status.3 L to R

Laboratory research Diabetes can cause 1 Paterson JM et al. Proc Natl Acad Sci USA into diabetes is helping damage to the retina. 2004; 101: 7088–93. to change treatments. Professor Andrew 2 da Silva Xavier G et al. Proc Natl Acad Sci USA Inês Barroso (right), Hattersley (left) examines 2004; 101: 8319–24. who is studying the role a patient’s eye. of the AKT2 gene in type 3 Scott JW et al. J Clin Invest 2004; 113: 274–84. 2 diabetes. KNOWLEDGE KNOWLEDGE 12 13 CROSS-CHANNEL DISSECTING TAILORED TREATMENT BALANCING THERAPY DIABETES ACTS Thanks to the discovery of the precise cause of infant diabetes, The mechanisms of type2 Two forms of diabetes respond very differently to drugs – pointing young children can be given medication rather than insulin injections. (adult-onset) diabetes are the way to tailored drug treatments based on genetic make-up. beginning to be unravelled.

With fears of an ‘obesity epidemic’ growing, it is crucial we learn more about the metabolic processes underlying our energy balance, and how they can trigger disease.

• The ‘metabolic syndrome’ (a combination of high blood pressure, insulin resistance and impaired lipid metabolism) is usually associated with obesity. An international team including Professors John Mullins and Jonathan Seckl in Edinburgh has shown that high levels of gluco- Permanent neonatal diabetes is reducing potassium loss and If the body’s tissues become The genetic make-up of patients They found that people with HNF-1α corticoid hormone regeneration in the a severe, but fortunately rare form depolarising the beta-cell membrane. insensitive to the action of insulin, with type 2 diabetes has been found diabetes responded differently to the liver can give rise to the metabolic of diabetes. The causes have been This causes an influx of calcium, rising blood sugar levels have a to affect their sensitivity to drug two drugs: patients with HNF-1α syndrome in the absence of obesity.1 largely unknown, but researchers which triggers the release of insulin. variety of damaging effects – leading treatments. The findings could lead diabetes had around a fivefold greater This could occur in people of normal have now found that many cases to the symptoms of type 2 diabetes. to more tailored treatments, and is response to sulphonylureas than to weight who have symptoms of are due to a genetic mutation that Professors Andrew Hattersley an early example of a pharmaco- metformin, while patients in the other metabolic syndrome, such as those disrupts control of insulin-releasing (Peninsula Medical School, Exeter) While most cases are thought to involve genomic approach to medicine. group responded similarly to the two with ‘fatty liver’ disease. beta cells.1 The research also and Frances Ashcroft (University interactions between many genes and treatments.1 The difference arose suggests that sulfonylurea drugs of Oxford) and colleagues found environmental risk factors, diabetes can Type 2 diabetes is an adult-onset because the response to sulphonylureas • A mammalian enzyme known as typically used by adults with type mutations in the gene encoding sometimes be caused by a mutation form of diabetes that frequently in HNF-1α patients was fourfold greater PASK is related to a bacterial oxygen 2 diabetes may be a useful treatment. Kir6.2, a key subunit of the potassium in a single gene. requires treatment with drugs. than in the second group, even though sensor, FixL. A team led by Professor channel, in ten out of 29 infants with The most commonly used drugs are the former used a lower drug dose Guy Rutter in Bristol has discovered In neonatal diabetes, a lack of insulin neonatal diabetes. The mutation stops Dr Inês Barroso (Wellcome Trust Sanger sulphonylureas or metformin, which to avoid hypoglycaemia. that PASK is also a sensor: in becomes apparent in the first three the channel responding to ATP, so Institute), Professor Steve O’Rahilly increase insulin secretion or reduce pancreatic beta cells, it responds months after birth. Insulin treatment it never closes totally. The beta cell (University of Cambridge) and colleagues insulin resistance, respectively. As the genetic basis of type 2 diabetes to glucose concentrations, regulating is required for life. constantly leaks potassium, and found just such a mutation in a gene Treatment guidelines assume that all is untangled, it is likely that further key beta-cell genes.2 PASK thus it cannot secrete insulin. called AKT2. AKT2 protein is a crucial patients respond similarly, even though different forms of the disease will be appears to play a role in the body’s Insulin is produced by beta cells in component of the cell’s systems for the underlying causes of the diabetes identified, each with a particular pattern response to changing nutrient levels. the pancreas, which sense changes Sulfonylurea drugs are known to act regulating cell growth, survival and may be quite different. of responses to diabetes drugs. If so, in the blood’s glucose levels, and alter on the KATP channel, and some patients metabolism. This study reveals its central drugs and the doses used could then • CBS domains are tandemly repeated their secretion of insulin accordingly. with mutant Kir6.2 did secrete insulin role in cellular responses to insulin.1 Professor Andrew Hattersley, Ewan be refined according to a patient’s 60 amino acid domains found in Crucial to this process is an ion channel when given such drugs. Follow-up Pearson and colleagues at the genetic background. most living organisms. Although – the ATP-sensitive potassium channel studies have confirmed that children with Mutations in AKT2 are unlikely to explain Peninsula Medical School, Exeter, mutations in CBS gene sequences 1 Pearson ER et al. Genetic cause (KATP channel) – that spans the Kir6.2 mutations no longer need insulin most cases of diabetes. A more likely compared the drug responses of people cause a range of inherited diseases, of hyperglycaemia and response to treatment membrane of beta cells. injections when given sulfonylurea drugs. scenario is that other subtle variations with a specific form of diabetes caused in diabetes. Lancet 2003; 362: 1275–81. the domain’s role has been unclear. in or around the AKT2 gene contribute by mutations in the HNF-1α gene with Professor Grahame Hardie and If glucose levels go up, more ATP 1 Gloyn AL et al. Activating mutations in the gene to the common form of diabetes. those in other patients who had colleagues at Dundee have now encoding the ATP-sensitive potassium-channel is made in the cell; this ATP binds subunit Kir6.2 and permanent neonatal diabetes. The team is now hunting for variants diabetes of unknown cause. shown that the domains bind to the channel and closes it, thereby N Engl J Med 2004; 350: 1838–49. in populations with type 2 diabetes adenosyl compounds (such as AMP, to explore this possibility. ATP or S-adenosyl methionine). In many cases, including AMPK, a key 1 George S et al. A family with severe insulin energy sensor in the body, the resistance and diabetes due to a mutation in AKT2. Science 2004; 304: 1325–8. domains appear to link the protein’s activity to the cell’s energy status.3 L to R

Human resources: meeting training and career development needs of researchers. Physical resources: building suitable conditions RESOURCES for research.

Wellcome-funded research fellows • Page 16: One danger is that source deficiencies in the UK’s academic have produced many exciting materials literally disappear. A special research infrastructure: research discoveries this year. Wellcome scheme is helping to Articles here summarise two ensure that irreplaceable papers • Page 18: Two internationally examples, both of which could are secured for future generations; significant facilities opened in Oxford have major medical implications: • Page 18: The Guildford Archiving this year. They are not just a better Project is ensuring that internal working environment but are also • Page 16: Huntington’s disease is tobacco industry papers remain changing the way scientists interact currently untreatable but a study in accessible on the web, a valuable and conduct research. mice has suggested a possible new resource for anyone studying therapeutic approach; industry tactics and behaviour. Finally, research itself generates • Page 17: Small offspring often go biological resources. Sharing these through ‘catch-up’ growth – which Through the Joint Infrastructure Fund provides a fillip for research: could affect their long-term health. and Science Research Investment Fund, two partnerships with the • Page 19: Genetic resources are Historians have quite different resource UK Government, the Wellcome Trust accelerating research on mouse needs from scientists: provided £450 million to tackle models and making the frog an even more useful tool. RESOURCES RESOURCES 14 15

Human resources: meeting training and career development needs of researchers. Physical resources: building suitable conditions RESOURCES for research.

A drug normally used to prevent The Cambridge researchers discovered Those who cannot remember the past, The collection includes some 37 000 Parents take pride in seeing their grew poorly in the womb, but were organ rejection could stop a toxic that rapamycin may be able to protect said philosopher George Santayana, case notes which provide a fascinating tiny newborns fill out into chubby subsequently suckled by mice on a protein accumulating in the brains the brain by cranking up ‘autophagy’ – are condemned to repeat it. Historical glimpse of day-to-day life on the wards toddlers. But for very small babies, high-quality diet. Their lifespans were of people with Huntington’s disease. one of the ways in which the cell can enquiry aims not just to remember the during a crucial period of change rapid ‘catch-up’ growth may not cut further if they ate obesity-inducing Researchers at the University of dispose of proteins. In their models, past but to understand it and, perhaps, in medicine. As such they help be as healthy as it seems – a study food after weaning. Cambridge, led by Wellcome Trust when used before too much toxic to ensure that we learn from it rather illuminate everything from changing of mice suggests it could actually Senior Research Fellow Dr David protein accumulated, rapamycin than repeat it. medical education to shifts in attitudes be shortening their lifespan.1 Low birth weight is already known Rubinsztein, have discovered that funnelled mutant huntingtin into towards experimentation on patients. to predispose to late-onset conditions the drug rapamycin reduces the compartments of the cell that digest it. The Research Resources in Medical Edinburgh was central to many The startling results were obtained by such as high blood pressure and effects of the Huntington’s disease History scheme was set up to ensure of these developments. Dr Susan Ozanne, a Research Career diabetes. These results suggest that mutation in cultured cells, fruit flies The researchers found that a rapamycin that significant collections are preserved Development Fellow,* and Professor the normal reaction to low birth weights and mice, raising hopes that it could analogue, CCI-779, slowed down and opened up for study, through use In an earlier project, the archive Nick Hales at the University of – a period of catch-up growth to bring be used to treat this nervous system neurodegeneration in a fly model of the of new conservation and preservation restored material from two other key Cambridge. They monitored the infants up to a normal size – may disorder in humans.1 disease, while in the mouse, it improved technologies and cataloguing. Some characters in Edinburgh medicine – longevity of mice whose mothers were contribute to these detrimental long- performance on four different £2 million has been awarded so far, Edwin Bramwell, widely regarded fed a poorly nutritious diet during their term effects. Huntington’s disease is a rare, inherited behavioural tasks. to support 58 projects. as the founder of Edinburgh fetal development or just after birth. disease characterised by abnormal body postgraduate medical education, They also tested the impact of a The results could have implications movements and impaired cognition; CCI-779 has the advantage that it is In Edinburgh for example, Lothian and Norman Dott, the first medic after ‘cafeteria-style’ diet after weaning. for babies born underweight, who are symptoms typically appear in designed for long-term use. The drug Health Services Archive has preserved Joseph Lister to receive the Freedom usually fed a rich diet to accelerate middle age. is currently in phase 2 and phase 3 the Royal Infirmary of Edinburgh case of the City of Edinburgh. The pups that lived longest were those growth. In view of the findings, the clinical trials for cancer, though more notes of two leading mid-20th century that were well fed in the womb and then researchers argue that more attention It is caused by a faulty gene that studies would be needed before human medics – Derrick Dunlop, Christison Without preservation, these collections suckled by mothers on a relatively low- needs to be paid to the nutrition of changes the huntingtin protein into trials were begun for Huntington’s. Professor of Therapeutics and Clinical might have been lost for ever – victim quality diet. Their lifespans were further human infants in the early years. a toxic product which accumulates in Medicine from 1936 to 1952, and to the ravages of time and rusty paper- enhanced if they were not given a the brain and interferes with brain cell 1 Ravikumar B et al. Inhibition of mTOR induces James Learmonth, University Professor clips. Now, historically valuable material cafeteria-style diet, rich in sugar and fat, 1 Ozanne SE, Hales CN. Lifespan: catch-up growth autophagy and reduces toxicity of polyglutamine and obesity in male mice. Nature 2004; function. There are genetic tests to expansions in fly and mouse models of of Surgery from 1939 to 1956, who has been carefully conserved and after weaning. 427(6973): 411–2. detect the faulty Huntington’s gene, but Huntington disease. Nat Genet 2004; 36(6): included George VI among his patients. secured for future generations. *Dr Ozanne is now a British Heart Foundation there is no cure or effective treatment. 585–95. At the other extreme, the pups that Lecturer at the University of Cambridge. lived the shortest lives were those that

L to R Rapamycin analogues An archivist from could help people with the Lothian Health Huntington’s disease. Services Archive. Paper-clips can cause A period of ‘catch-up’ significant damage growth for underweight to archive collections. newborns could damage their long-term health. RESOURCES RESOURCES 16 17 HUNTINGTON’S HOPE SHELF CATCH-UP GROWTH PRESERVATION Work on fruit flies and mice has identified a potential Material relating to key figures in Feeding up lightweight babies may be storing therapeutic strategy for Huntington’s disease. Edinburgh’s distinguished medical up longer-term problems. history has been preserved.

L to R Rapamycin analogues An archivist from could help people with the Lothian Health Huntington’s disease. Services Archive. Paper-clips can cause A period of ‘catch-up’ significant damage growth for underweight to archive collections. newborns could damage their long-term health. RESOURCES RESOURCES 18 19 OPENING TIME TOBACCO ARCHIVE SHARING SUCCESS BEYOND THE HELIX The Wellcome Trust’s recent A massive photocopying operation is ensuring a tobacco Resources created for a laboratory’s own research infrastructure investment giant’s inner workings will remain in the public domain. are also being shared to benefit the wider community. is now bearing rich fruit.

We now know that humans have only about 23 000 genes. Our biological complexity is thus more to do with how those genes are used – how and where they are turned on and off. Many different mechanisms of gene control are being discovered – and the higher- order arrangement of DNA is turning out to be particularly important.

• In budding yeast, Professor Nick Proudfoot and colleagues at the University of Oxford found that the DNA of active genes was not linear, Seventeen new buildings funded A website containing 1 million pages Information currently on the new website Studies in model organisms are The African clawed frog Xenopus laevis as typically drawn in textbooks, but by two high-profile Wellcome Trust of formerly secret documents from relates to company practice from the providing many insights into the has long been a favourite of biologists. was looped, with control proteins partnerships with the UK Government the world’s second-largest tobacco early 1900s to the mid-1990s. Internal biological roles of genes. Thanks to Unfortunately, having a duplicated shared between the start and end – the £750 million Joint Infrastructure company, British American Tobacco correspondence, research and reports genome sequencing projects, gene- genome, it is not good for genetic points of the gene. This looping was 1 Fund (JIF) and £1 billion Science (BAT), went online in October 2004. offer a unique insight into the strategies based approaches are wildly popular. studies, and it takes more than a year essential to the activation of the gene. Research Investment Fund (SRIF) – Researchers and the public will now used by tobacco companies to promote Now, new techniques are being to reach sexual maturity. Conveniently, • RNA interference (RNAi) is an exciting were opened or occupied during the have free and unfettered access to themselves and their products, including developed to enable even greater Xenopus tropicalis is diploid and area of study, as these tiny RNAs year. Two buildings in Oxford illustrate information relating to BAT’s activities, influencing scientific research and public use to be made of genomic reources. matures in just four months. can silence genes very effectively. how new facilities are supporting which reveal disturbing evidence policy, targeting marketing, advertising Generally, they act by triggering larger-scale and more integrated of the industry’s efforts to thwart and promotion activities at young At the Wellcome Trust Sanger Institute, To speed up research into X. tropicalis a massive destruction of the RNA approaches to biomedical research. anti-smoking initiatives and market people and women, and the strategic Dr Allan Bradley’s team has developed – a field that is still in its infancy – intermediate (messenger RNA) read cigarettes to vulnerable populations. exploitation of cigarette smuggling. a technique to speed up research on Dr Enrique Amaya, Dr Nancy from a gene, but Dr Vera Schramke In February 2004, HRH The Queen and The documents reveal how BAT has mice. To explore the function of a gene, Papalopulu and Professor Jim Smith and Professor Robin Allshire, a HRH The Duke of Edinburgh officially The website is a joint project, known targeted emerging markets in the researchers often study the effects at the Wellcome/Cancer Research Wellcome Principal Research Fellow opened the new £60 million Chemistry as the Guildford Archiving Project, developing world, including, for of mutations that disrupt or change UK Gurdon Institute in Cambridge, in at the Wellcome Trust Centre for Cell Research Laboratory at the University between the London School of Hygiene example, its intention to market to the gene. Producing such mutations collaboration with the Sanger Institute, Biology, University of Edinburgh, have discovered that small RNA molecules of Oxford. With nearly 17 000 square and Tropical Medicine, the University “dirt poor little black farmers” and “low can be time-consuming, however. have sifted through more than can somehow drive the formation metres of laboratory and office space, of California San Francisco and the income low literacy” people in South 200 000 fragments of the X. tropicalis of ‘closed’, tightly packed DNA 3 it is one of the largest research Mayo Clinic. BAT was forced to make Asia and the Middle East. Dr Bradley’s team has developed a new genome and identified 7000 genes. conformation and shut down genes.2 departments in the world. Facilities the documents public in 1998 after high-throughput method to alter genes Full-length clones are available through include 11 nuclear magnetic resonance a legal settlement by a US court against Crucially, the site will preserve the – MICER (Mutagenic Insertion and the MRC Geneservice, while the • A collaboration led by Dr Nigel Carter machines, 11 mass spectrometers and a number of tobacco companies. collection beyond 2009, when BAT Chromosome Engineering Resource). Gurdon Institute has also produced at the Wellcome Trust Sanger Institute an X-ray crystallography facility. The settlement ruled that all corporate is allowed to close the depository. The MICER resource1 consists of a database describing the sequences and Dr Wendy Bickmore at the MRC documents submitted during the a large collection (library) of DNA and associated genomic information. Human Genetics Unit in Edinburgh In September 2004, Nobel Prizewinner ‘discovery’ process for the case must The Guildford Archiving Project has been funded fragments, corresponding to parts has examined DNA conformation by the Wellcome Trust, the Flight Attendant across the entire human genome. James Watson opened the Henry be made available via two archives, one Medical Research Institute, Cancer Research of mouse genes, which can be used Such resources should help kick-start Wellcome Building of Gene Function. at Guildford, UK (operated by BAT), and UK, Health Canada and the American Heart to target and disrupt mouse genes a potentially valuable field of research As expected, active genes lay in regions of open chromatin, and The new £19 million building has the other at Minnesota, USA (operated Association. The BAT document archive website (or even insert specific new sequences). and add to the pantheon of can be accessed at www.bat.library.ucsf.edu inactive genes in tightly packed been designed to encourage greater by an independent paralegal firm). Some 100 000 different MICER vectors experimental organisms used chromatin. But there were exceptions: interaction between researchers are available from the Sanger Institute. in research around the globe. some genes in open chromatin were in genetics, human anatomy and Another technical advance from the inactive, while some in compact physiology and experts in important Bradley lab makes these vectors even 1 Adams DJ et al. Mutagenic Insertion and 3 Chromosome Engineering Resource (MICER). chromatin were active. new fields such as bioinformatics more useful. Mammalian cells carry Nat Genet 2004; 36(8): 867–71. and biostatistics. two copies of each gene, and the new 2 Guo G, Wang W, Bradley A. Mismatch repair 1 O’Sullivan JM et al. Nat Genet 2004; 36(9): L to R method ensures that both copies genes identified using genetic screens in Blm- 1014–8. Aerial view of the new Allan Bradley 2 deficient embryonic stem cells Nature 2004; 2 Schramke V, Allshire R. Science 2003; 301: This will allow researchers to mount chemistry labs at Oxford. of the Wellcome Trust are disrupted. 429(6994): 891–5. 1069–74. a united effort to discover how genes Nuisance smokers, Sanger Institute. 3 Gilchrist M et al. Defining a large set of full 3 Gilbert N et al. Cell 2004; 118(5): 555–66. cause disease – and to focus on by Henry Heath, 1827. Research on mice Meanwhile, researchers in Cambridge length clones from a Xenopus tropicalis EST ground-breaking treatments for many is providing valuable have launched a new genomics project. Dev Biol 2004; 271: 498–516. insight into important (www.gurdon.cam.ac.uk/informatics/ important diseases. biological processes. resource for the frog Xenopus tropicalis. Xenopus.html) RESOURCES RESOURCES 18 19 OPENING TIME TOBACCO ARCHIVE SHARING SUCCESS BEYOND THE HELIX The Wellcome Trust’s recent A massive photocopying operation is ensuring a tobacco Resources created for a laboratory’s own research infrastructure investment giant’s inner workings will remain in the public domain. are also being shared to benefit the wider community. is now bearing rich fruit.

Promoting patient-oriented and health services research. Advancing the dissemination and exploitation of the results of Trust-funded research. TRANSLATION

‘Translation’ is all about making a Malaria continues to exact a The most direct benefits, of course, practical difference – generating and devastating toll, particularly among come from studies on patients. using new knowledge to provide health young children in Africa. Around 3000 Wellcome-funded clinical research benefits to people. There are many children in Africa die every day. Clinical is continuing to suggest and test ways in which those benefits may research is tackling several aspects new therapies, in the UK and in be realised: of the disease: developing countries:

• Page 22: Genetic analysis of cancers • Page 24: Artemisinin combination • Page 26: In Vietnam, steroids have is revealing new drug targets; therapy – drug treatment pioneered been shown to enhance survival after • Page 22: A ‘dipstick’ diagnostic tool in South-east Asia – could have a tuberculous meningitis infection; for Chlamydia is being taken up and major impact if widely used in Africa; • Page 26: In the UK, the Wellcome used, and adapted for other • Page 24: Unravelling the complex Trust’s Clinical Research Facilities infections; immune response to the have begun to deliver a stream • Page 23: Field tests of malaria malaria parasite; of important findings and are having diagnostic kits confirm their • Page 25: How the parasite becomes a significant local impact; practical value; resistant to the antimalarial • Page 27: The ‘Myskin’ smart • Page 23: Studies of deadly avian flu drug mefloquine; dressing was launched during are helping us prepare for further • Page 25: Why cerebral malaria isn’t the year for burns patients. outbreaks. always what it seems. TRANSLATION TRANSLATION 20 21

Promoting patient-oriented and health services research. Advancing the dissemination and exploitation of the results of Trust-funded research. TRANSLATION

The Cancer Genome Project at the trastuzumab (marketed as Herceptin) The rapid testing technology created A trial of two malaria diagnostic kits People infected with the deadly avian in 1918. It is vital, therefore, that we Wellcome Trust Sanger Institute has, targets ERBB2 and is very effective by Dr Helen Lee and colleagues at the has shown that error rates are low and influenza virus strain H5N1 were learn as much as possible about the for the first time, identified mutations for the treatment of breast cancers University of Cambridge has moved that they can be used with minimal treated and studied at Wellcome- virus and its effects on people. within the ERBB2 gene in human lung with multiple copies of the ERBB2 on apace since the team completed training.1 These kinds of diagnostic supported facilities in Vietnam. Having cancer.1 The mutations, found in gene. Previous trials of trastuzumab the development of its Chlamydia tests thus seem highly suitable for use excellent clinical and laboratory The Hospital for Tropical Diseases and 10 per cent of a specific type of for lung cancer were not successful, ‘Firstburst’ dipstick a year ago. in the field. facilities in a country directly affected the Clinical Sciences Research Institute lung cancer called adenocarcinoma, but the Cancer Genome Project team by avian flu is an enormous benefit supported by the Wellcome Trust in cause the ERBB2 protein to be proposes that it, or another drug that This rapid test provoked interest Diagnosing malaria quickly can make with a disease that is so rapidly Ho Chi Minh City was chosen by the permanently active. These cancers targets ERBB2, should be retested from organisations around the world, a huge difference to the treatment lethal and of such global public Vietnamese government as the national may be treatable with an existing in cases of lung adenocarcinoma including the American Red Cross, of the disease. The standard method health importance. centre for admission of all suspected drug, trastuzumab. with ERBB2 mutations. a major pharmacy chain, as well as a of diagnosis, looking at blood smears cases and for the clinical and scientific number of diagnostic companies and under the microscope to spot parasites, During late 2003 and early 2004, analysis of the virus. The detailed The Cancer Genome Project team This finding follows the team’s discovery non-profit organisations that deal with is time-consuming, expensive and the avian influenza virus H5N1 swept examinations of ten patients infected is cataloguing the changes within the in 2002 that the BRAF gene is mutated women’s sexual health. The first-void requires extensive training. through poultry stocks across Asia. with the virus (eight of whom died) genomes of cancer cells and identifying in 70 per cent of cases of malignant urine collector the group developed Most worryingly, it also spread to some were published by the New England the mutant genes responsible for the melanoma, a potentially lethal form received the Best Medical Futures With help from the Wellcome Trust’s people, causing a severe and often fatal Journal of Medicine,1 and the speed disease. Lung cancer is a particularly of skin cancer. The mutations appear Diagnostic Innovation award. research programme in Thailand, respiratory illness. of publication – only a few weeks after important target, as it is the second to produce a permanently activated Dr Mayfong Mayxay and colleagues the patients were admitted to hospital – most common form of cancer in the BRAF protein. With Wellcome Trust The Chlamydia rapid test was recently in rural Laos have trialled two tests, There are constant fears that this strain highlights the value of combining UK, after breast cancer. Technology Transfer funding, the team adapted to detect trachoma, an eye ParacheckPf and OptiMAL, which use will spread from birds to humans. clinical and scientific expertise in has been searching for molecules that disease that affects 150 million people ‘dipsticks’ to test blood samples for the An even greater worry is that the virus a single institution. The ERBB2 gene (also known as HER2 can switch off the mutant protein – and worldwide and causes 6 million cases presence of proteins from the parasite. adapts to human hosts, and begins or Neu) is present in multiple copies in several promising leads have emerged. of blindness or visual impairment. Field After one hour of training, 64 village to be transmitted from person to person 1 Hien TT et al. Avian influenza (H5N1) in 10 patients in Vietnam. New Engl J Med 2004; 20 per cent of breast cancers and less trials on schoolchildren in Tanzania have health volunteers, with no previous – in a manner similar to the ‘Spanish flu’ 350: 1179–88. often in other cancers. The discovery 1 Stephens P et al. Lung cancer: intragenic ERBB2 produced excellent results. laboratory experience, performed two kinase mutations in tumours. Nature 2004; 431: that ERBB2 mutations can also cause 525–6. different tests accurately. lung cancer is significant as the drug Now Dr Lee’s Diagnostics Development Unit, based at Addenbrooke’s Hospital, The researchers then followed six is developing a triplex rapid test capable volunteers over ten months to check of detecting HIV, hepatitis B and the accuracy of the testing and how hepatitis C viruses in the same sample. often retraining was required. Error The test, supported by a Wellcome rates were extremely low compared Technology Transfer Award, will be to microscopy (less than 2 per cent), used to improve blood safety in and minimal training was required. L to R developing countries. Melanoma cells: Anopheles gambiae, 70 per cent of malignant which transmits 1 Mayxay M et al. An assessment of the use melanoma are caused the malaria parasite. of malaria rapid tests by village health volunteers by BRAF mutations in rural Laos. Trop Med Int Health 2004; 9: Poultry is the main host 325–9. Helen Lee and her team of the avian flu virus. at Cambridge have There are fears that an developed a rapid test avian flu epidemic could to detect chlamydia. begin in South-east Asia. TRANSLATION TRANSLATION 22 23 GENE TARGETS TESTING FIELD TEST FLU FEARS TIMES The identification of genes responsible for particular forms The dipstick diagnostic test for Handy diagnostic tests for malaria South-east Asia needs its own local high-quality of cancer is opening up the possibility of targeted cancer therapies. Chlamydia is being widely adopted. can be used easily in the field, new clinical centres to tackle the perils of avian flu. research suggests.

ACT NOW FIGHTING BACK EJECT AND ASSESSING MALARIA SURVIVE An analysis of clinical trials with Models suggest how the malaria parasite evades the human immune The genetic basis of mefloquine Deadly cerebral malaria is difficult to diagnose and is poorly artemisinin combination therapy system so successfully, and new hope for a malaria vaccine. resistance has been revealed. understood. Research in Malawi is providing a clearer picture. has confirmed its enormous value.

Artemisinin combination therapy The human immune system wages responses are produced against the Resistance to the antimalarial drug Plasmodium falciparum, the most The only clinical way of distinguishing (ACT) – the use of artemisinin or war against the malaria parasite as entire variant repertoire, and the mefloquine, introduced in Thailand dangerous malaria parasite, spends malarial from non-malarial coma was related compounds along with a it tries to eradicate an infection. infection ends. in 1984, took just six years to develop. part of its life multiplying within red to examine the eye – almost all of those second antimalarial drug – has been Having identified parasite proteins, Researchers have now discovered blood cells. Later on, infected cells with malarial coma had damage to the pioneered by Professor Nick White the system ramps up production Meanwhile, in their quest to develop how the parasite became resistant become ‘sticky’ and adhere to the capillaries in the retina. and colleagues at the Wellcome Trust’s of antibodies that will help kill the a malaria vaccine, Professor Adrian Hill to the drug – by duplication of a key walls of blood vessels; when this South-east Asia Major Overseas parasite; the parasite’s response is (University of Oxford) and colleagues parasite gene. occurs in the brain, as it does in about Another study by Professor Molyneux Programme. Extensive trials have to change its proteins. But possibly have been studying parasite proteins 1 per cent of cases, cerebral malaria and colleagues in Malawi and France shown that ACT is safe and effective. not too much, a new mathematical that induce an immune response. One Dr Ric Price (a Wellcome Career and coma result. Even with the best identified a second feature peculiar The Thai unit has published nearly model suggests. problem facing vaccine researchers is Development Fellow in Clinical Tropical treatments, 15–20 per cent of children to children with severe malaria – much 10 per cent of all antimalarial drug that while proteins have been found that Medicine), Professor Sanjeev Krishna in such comas will die. higher levels of tiny particles derived trials since 1966, enrolling more than The models, produced by a do stimulate an immune response, none (St George’s Hospital Medical School, from the lining of blood vessels.2 20 per cent of patients. collaboration between researchers so far has led to protection against London), Professor Nick White and In reality, it is not easy to tell whether in Oxford, Edinburgh and Kenya, natural malaria infection. Dr François Nosten (Wellcome a child in a coma has cerebral malaria Parasitised red blood cells attach to this Derived from the plant Artemisia annua, examine the parasite’s PfEMP1 Trust–Mahidol University–Oxford or some other coma-causing illness. lining, usually in deep, inaccessible artemisinin and its derivatives are now receptors, proteins that it inserts In studies in The Gambia, the Tropical Medicine Research In addition, the effects on the brain tissues. These particles may therefore widely used in South-east Asia. into the surface of red blood cells researchers have tested a new Programme, Thailand) and colleagues are not well defined. be an indicator that infected cells are To reduce the risk of resistance, while it is reproducing inside. This candidate that includes part of the have studied patients in the Karen collecting in vital organs. combination treatments are preferred. protein is a prime target for the parasite’s circumsporozoite protein, community living in a malarious hill To investigate, Professor Malcolm In 2004, the International Artemisinin immune system, but with more than which it produces in its sporozoite forest on the northwestern border Molyneux (Malawi–Liverpool–Wellcome 1 Taylor TE et al. Differentiating the pathologies of cerebral malaria by postmortem parasite Study Group reported a meta-analysis 50 variants the parasite can switch stage – the stage that is injected into of Thailand. This harbours the world’s Trust Cinical Research Programme) counts. Nature Med 2004; 10: 143–5. to assess the value of artesunate when to a new type, allowing it to prolong the bloodstream by a feeding mosquito. most multidrug-resistant Plasmodium and colleagues in Malawi, the UK and 2 Combes V et al. Circulating endothelial added to other drugs. Pooling data the infection. falciparum parasites. USA conducted autopsies on 31 microparticles in Malawian children with severe falciparum malaria complicated with coma. from 16 studies and nearly 6000 They found that while several portions children who had been diagnosed J Am Med Assoc 2004; 291: 2542–4. patients, they found that the addition The new model suggests that each of the circumsporozoite protein induced They found that resistance to mefloquine with cerebral malaria. They found, This study was funded by the Wellcome Trust, of artesunate had significant benefits.1 variant elicits two types of immune an immune response, one fragment in was associated with extra copies of surprisingly, that although all the the French Ministry of Research, the PAL+ 1 Programme, and the UNDP/World Bank/WHO response: a long-lived response directed particular was associated with a longer- a Plasmodium gene known as pfmdr1. patients had parasites in their brains, Special Programme for Research and Training Since 2001 the World Health against that protein alone; and minor, lasting immune protection against The gene codes for a molecular pump seven of them (23 per cent) had in Tropical Diseases. Organisation has increasingly promoted short-lived responses that target parts malaria.2 This, they suggest, makes it a that ejects the drug from the parasite actually died from other causes.1 ACT, recommending that any country of the protein shared by more than one good option to include in new vaccines. cell before it has a chance to do any changing antimalarial treatment policy protein.1 The latter responses delay harm. Presumably, the more copies should switch to ACT. Over 20 countries the appearance of variants with similar 1 Recker M et al.Transient cross-reactive immune of the pfmdr1 gene that a parasite has, responses can orchestrate antigenic variation have switched, and many others have shared portions. So the switching in malaria. Nature 2004; 429: 555–8. the more pump protein the parasite L to R begun to change. The latest study occurs sequentially, each new variant 2 Reece WH et al. A CD4(+) T-cell immune makes – and the more likely it is to reinforces how valuable the therapy being the most immunologically distinct response to a conserved epitope in the survive treatment with mefloquine. Artemisia annua, Kenyan children, circumsporozoite protein correlates with a source of agents for whom malaria could be in a continent in which malaria from its preceding types. As a result, protection from natural Plasmodium falciparum used to treat drug- is an everyday scourge. is threatening to run away unchecked. the overall duration of infection is infection and disease. Nature Med 2004; 10(4): 1 Price RN et al. Mefloquine resistance resistant malaria. A malaria-infected in Plasmodium falciparum and increased pfmdr1 increased; eventually, long-lasting 406–10. Kevin Marsh, head red blood cell. copy number. Lancet 2004; 364: 438–47. of Wellcome’s research 1 International Artemisinin Study Group. Artesunate Professors Peter combinations for treatment of malaria: meta- programme in Kenya. Winstanley (left) and analysis. Lancet 2004; 363: 9–17. Malcolm Molyneux. TRANSLATION TRANSLATION 24 25

The Wellcome Trust–Burroughs Wellcome Fund Infectious Diseases Initiative, launched in 1999, brought together researchers from the UK, North America and the developing world. The initiative aimed to provide large-scale, long-term support for trilateral partnerships, in which the centre of gravity would be in the developing country. Some 13 projects were funded, to the tune of £18 million (US$27 million), based in Asia, Africa and South America.

Tuberculosis is usually associated Wellcome Trust Clinical Research The CRFs have been used as a model Skin grafting is the first-line treatment robust than other methods, which take While many projects are at early with lung disease. But its cause, Facilities (CRFs) were set up for other similar facilities set up around for burns but sometimes, in severe up to two to three weeks to grow the stages, they have clearly delivered Mycobacterium tuberculosis, can also to provide a specialist hospital the country. cases, there is not enough skin to go cells and involve a much more major benefits to the participants invade other parts of the body, such environment dedicated to research round. CellTran, a start-up company complicated process. Myskin also and host institutions, and in some as cerebrospinal fluid. The resulting involving people. A review of progress Evidence of the success of the venture based in Sheffield and a recipient marks the first time cells have been cases have had a direct impact inflammation (tuberculous meningitis) has revealed that all five CRFs have also comes from the steady stream of Wellcome Technology Transfer placed directly onto a patient’s wound on public health. causes death or severe neurological established effective infrastructure of research papers coming out of the funding, has come up with a solution: via a bandage. problems in more than half of those and management systems. High- CRFs. Among the many important Myskin, ‘living bandages’ containing • A study in Bangladesh on the causes, affected. Research in Vietnam, quality research is being carried out studies are the following: the patient’s own skin cells. Myskin was launched for the treatment prevention and treatment of neonatal however, has shown that steroid use within them. And they are also playing of severe burns in April 2004 at the infections in the community has significantly reduces mortality. influential roles locally and nationally. Birmingham: Cannabinoid therapy for The skin cells are usually taken from British Burns Association, Manchester. raised the profile of neonatal multiple sclerosis; antibody therapy for the thigh, under local anaesthetic, CellTran has partnered with a UK healthcare locally. The research has Reasoning that corticosteroids might The CRFs – at Birmingham, vasculitis; gene therapy for liver cancer. and then transferred to a small polymer distribution partner, Vernon Carus, fed into national policy making, while reduce inflammation, a team led by Guy Cambridge, Edinburgh, Manchester disc, coated with a chemically controlled a Top 50 NHS supplier, so the product a training manual in newborn care Thwaites at the Pham Ngoc Thach TB and Southampton – were established Cambridge: Genetic causes of obesity; plasma polymer film which promotes is easily available within the NHS. is being adopted at a national level. and Lung Hospital, the Hospital for as partnerships between the Wellcome neurochemical impact of drug abuse; the growth of skin cells. After five Tropical Diseases and the Oxford Trust, the Department for Health, immune response to respiratory to seven days, the discs are placed CellTran has begun a large clinical trial • In Vellore, India, a project on rotaviral University Clinical Research Unit, Ho and the Scottish Executive. syncytial virus in children. directly onto the wound and the area of Myskin’s effects on diabetic ulcers, gastroenteritis in children has had Chi Minh City, ran a trial of the steroid is wrapped in bandages. The polymer and preliminary studies have shown that an unexpected benefit – a substantial dexamethasone plus antibiotics in 545 As well as hosting valuable research, Edinburgh: Impact of air pollution film is engineered to release the cells it works well on difficult-to-heal wounds. decrease in infant mortality in the patients in Vietnam.1 the CRFs are having wider influence, on cardiovascular disease; genetic when exposed to the wound, thus urban slum in which it was based, becoming recognised regional centres susceptibility to cardiovascular disease helping new layers of skin to grow. CellTran Ltd has been funded by the as field workers now recognise The trial showed that additional of clinical research excellence. They in a rural population of Orkney. Wellcome Trust, Sheffield University illness and refer it to the project’s treatment with dexamethasone reduced act as beacons of best practice for There is a strong surgical need for Enterprises Ltd, and the White Rose local clinic. mortality (although it did not reduce governance and ethics, have developed Manchester: Using pelvic floor this kind of device. CellTran’s new Technology Seedcorn Fund. the risk of severe disability after nine strong collaborative links with local exercises to tackle stress technology is faster, simpler and more • The Peruvian cysticercosis project months). The steroids not only reduce NHS R&D offices, and created local incontinence; molecular genetics is studying infection with the inflammation, but may also reduce the educational programmes targeted of autoimmune disease. intestinal tapeworm Taenia solium, risk of other severe problems, such as at clinical researchers in their areas. which forms cysts in both humans potentially fatal clinical hepatitis, which The Edinburgh facility now also hosts Southampton: Management of hepatitis and its intermediate host, the pig. would have forced doctors to change a regional centre of the National C virus infection; effects of low birth The team is also testing candidate the antibiotic therapy. Translational Cancer Research Network. weight on infant lung function. vaccines, with spectacular success: the vaccines provide more than The work has led to changes in One notable feature has been the One future challenge is to identify L to R 99 per cent protection. The project treatment guidelines for managing development of a strong network of ways to capitalise on this initial success Mycobacterium The Edinburgh Clinical team has now been awarded tuberculous meningitis. nurse managers around the CRFs, as to strengthen clinical research in the UK. tuberculosis, which Research Facility building. US$15.5 million by the Bill and can cause tuberculous CellTran has developed well as a growth in nurse-led research. meningitis. ‘living bandages’ to treat Melinda Gates Foundation to 1 Thwaites, G et al. Dexamethasone Body fat scanning severe burns. evaluate a cysticercosis elimination for the treatment of tuberculous meningitis equipment at the programme in an area of Peru. in adolescents and adults. N Engl J Med 2004; Cambridge Clinical 351(17): 1741–51. Research Facility. TRANSLATION TRANSLATION 26 27 STEROID CLINICAL ADVANCES LIVING BANDAGES OF PIGS SUCCESS AND PEOPLE Steroids help people survive As well as hosting valuable patient-oriented research, Clinical An innovative product launched this year a tuberculous meningitis infection. Research Facilities are having important regional influence. will provide a new option for burns victims.

PUBLIC Stimulating an informed dialogue to raise awareness and understanding of biomedical science, its achievements, applications and implications. ENGAGEMENT

Public engagement aims to build Bridge building can take many forms: • Page 32: Innovative medical training bridges between scientific and other at the Peninsula Medical School communities. The language, concepts • Page 30: ‘Medicine in Context’ shows how the sciences can gain and accumulated knowledge of exhibitions at London’s Science from the arts; science can be daunting, and present Museum, such as this year’s on pain, • Page 32: The Eden Project has obstacles to the wider public sharing have provided unique interpretations benefited from a visitor centre grants in the excitement (and frustrations) of of fascinating topics; scheme to rejuvenate its exhibits; modern science, or joining debate into • Page 30: The Engaging Science • Page 33: The poignant Foundling its possible implications or application. Programme has brought new blood Museum is a reminder of the social into the field, with fresh ideas and context in which medicine is delivered. By the same token, separating science enthusiasm; from other aspects of modern life will • Page 31: The award-winning ‘Living The experience gained from these surely impoverish the discipline – and Dying’ exhibition at the British and other projects will be invaluable particularly one with such a human Museum illustrates how different as plans are laid for a new public dimension as biomedicine. cultures perceive their health; venture at 183 Euston Road, London, due to open in 2006. PUBLIC ENGAGEMENT PUBLIC ENGAGEMENT 28 29

PUBLIC Stimulating an informed dialogue to raise awareness and understanding of biomedical science, its achievements, applications and implications. ENGAGEMENT

“Beautifully organised... intelligently Pain: Passion, compassion, sensibility, Since its launch in September 2003, fingerprinting – to an event for members Living and Dying – the first exhibition the medicines a typical British man and curated… The exhibition weaves curated by Professor Javier Moscoso, the Engaging Science Programme has of the local community, schools and in the Wellcome Trust Gallery at the woman take during their lives, stitched between the witty, the horrific, the explored the ceaselessly shifting cultural enabled a diverse range of people and the university. British Museum, London – explored into two 13-metre pieces of fabric challenging and the banal.” This place of pain, and how science and organisations to get involved in public the different ways in which people mesh. These are surrounded by family was The Spectator’s verdict on Pain: other ways of thinking have shaped engagement. At the other end of the scale, Society around the world seek well-being photographs with handwritten captions, Passion, compassion, sensibility – our beliefs and responses to it. Awards support research or significant for themselves or their communities, and various medical objects, such as a Wellcome Trust exhibition at the The £3 million programme has been public activities – and focus on specific and how they deal with the harsh a mammogram, an X-ray and a Science Museum. Reflecting the compelling nature of the geared around flexibility, with small, areas of public engagement. Young realities of life. hearing aid. exhibition, the CD-ROM catalogue for fast-turnaround People Awards offering people’s education was a theme through The exhibition – which attracted nearly Pain was short-listed for the 2004 AXA the chance for people to turn ideas into 2004, and was the focus of a £415 000 Different societies have different Living and Dying, which opened in 100 000 visitors – highlighted how, Art Exhibition Catalogue Award. action and larger Society Awards Society Award to the science centre understandings of the causes and November 2003, won a prestigious despite its universality as a human available for bigger, longer-term and At-Bristol. symptoms of sickness, and different Museums and Heritage Show 2004 experience, the meaning of pain Pain and other Science Museum nationally important ventures. A whole ways of averting or confronting sorrow Award for Excellence for best has changed over time and across exhibitions have provided evidence of range of applicants has been tempted A team from the centre will work closely or need. This diversity is reflected in permanent exhibition. different cultures. a wide public enthusiasm for a ‘culturally to apply – including health practitioners, with teachers and a range of experts the objects produced by different integrated’ view of biomedical science. community workers, teachers, (including scientists, policy makers and cultures. Living and Dying dramatically The Wellcome Trust Gallery at the British Pain has variously been seen as a This approach will be picked up further postgraduate students, as well as consumer group representatives) to illustrated this fascinating diversity Museum will house a series of long-term means of salvation, a route to self- in the redeveloped Wellcome Building, academics and science communicators. develop a suite of tools that teachers with material from all over the world – exhibitions examining life’s challenges enhancement – or a sign of injury or due to open in 2006, which will be And quirky or ‘off-beat’ projects have can use to get young people thinking from the Andes to Zimbabwe. and the ways people from different illness. People’s responses to pain vary a public venue dedicated to the been supported as well as the worthy. and talking about science and its wider cultural backgrounds deal with them. accordingly: sometimes we suffer it, exploration of science and its social impact. New techniques might include The centrepiece of the exhibition, Using objects from vastly different times sometimes we contemplate or study it, and historical contexts. The year’s smallest award, for example, video conferencing, drama and filming, however, had its roots closer to home. and places as a window onto common and sometimes we try to alleviate it. At went to Dr Jonathan Cox, a postdoc at role-play, internet research tasks and The specially commissioned art human experience, the gallery will offer other times, willingly or not, we inflict it. the University of Bath. His People Award ethics committees. The most successful installation, ‘Cradle to Grave’, a distinctively fresh perspective on the of £786 enabled him to bring Sir Alec approaches will be disseminated widely produced by the Pharmacopoeia outstanding ethnography collections Jeffreys – the inventor of DNA within the UK’s teaching community. collective (artists Susie Freeman and of the British Museum. David Critchley, and GP Liz Lee), resembles a shop counter, running The Pharmacopoeia collective was formed thanks to one of the Wellcome Trust’s first-ever Sciart the length of the gallery. Inside, it shows awards. www.pharmacopoeia-art.net

L to R ‘Ecce homo’ by Nicholás at the Theatre Royal de Bussy, a centrepiece Plymouth are involved of the Pain exhibition. in a drama project funded Leg amputation in the by a Society Award. 18th century, by Thomas The Living and Dying Rowlandson. exhibition in the Playwright Simon Turley Wellcome Trust Gallery and Rebecca Gould at the British Museum. PUBLIC ENGAGEMENT PUBLIC ENGAGEMENT 30 31 PLEASURE AND PAIN GREAT AND LIVING AND DYING SMALL Combining art, history and science at a scientific venue – London’s Projects of vastly different scales Beautiful objects from all over the globe illustrate how different Science Museum – has proven a popular mix. have been funded through the new cultures perceive and protect their health and well-being. Engaging Science Programme.

L to R ‘Ecce homo’ by Nicholás at the Theatre Royal de Bussy, a centrepiece Plymouth are involved of the Pain exhibition. in a drama project funded Leg amputation in the by a Society Award. 18th century, by Thomas The Living and Dying Rowlandson. exhibition in the Playwright Simon Turley Wellcome Trust Gallery and Rebecca Gould at the British Museum. PUBLIC ENGAGEMENT PUBLIC ENGAGEMENT 32 33 MEDICAL PARADISE GAINS FOUNDLING FATHER A DRAMATIC INNOVATION YEAR Art is well known to benefit from Cornwall’s Eden Project aims to combine science, art and drama A new exhibition provides an insight into the lives of abandoned science. Less well appreciated to create a rich sensory experience for its visitors. children in the eighteenth century. is that science can gain from art.

Drama is highly effective at engaging young people, providing a way in for students who may be put off by ‘pure’ science. And it provides much inspiration for people whose first interest is in the performing arts.

• Many Pulse performances took place during the year. Among the most notable performances, the Trestle Theatre Company premièred their puppetry work, The Smallest Person, at the Edinburgh Fringe festival – “Visually ingenious and delightful”, Working with artist Helen Storey – The Eden Project site is dominated approaches to tackle scientific issues. Visitors to London’s Foundling no public places for artists to exhibit, said the Guardian – while students on a Sciart project exploring the nature by 2.2 hectares of covered ‘biomes’, In 2002 it hosted an exhibition of Museum, which opened in June so the Foundling Hospital became from Sir John Colfox School in of creativity – was a life-changing themed around tropical and the dresses produced by the Sciart 2004, can learn the remarkable story the first British public art gallery. Bridport collaborated with hospital episode in Professor John McLachlan’s Mediterranean landscapes, alongside partnership of Helen and Kate Storey, behind the Foundling Hospital, staff and artists to create an life. He was strongly struck by the a further 15 hectares of outdoor which were inspired by early which, like an early-day Live Aid, In the 1920s the Foundling Hospital imaginative and occasionally surreal humanising influence of art. And being temperate displays. The adjacent embryonic development. used artistic creativity to publicise was demolished, but its artistic site-specific work, Visiting Time, responsible for developing the courses Visitor Centre contains exhibits that shocking social ills. treasures were saved and moved performed at a variety of locations at the new Peninsula Medical School explore contemporary issues in And it has actively drawn upon drama to 40 Brunswick Square. The Foundling within Dorset County Hospital. (PMS), he was also able to put theory science, especially relevant to food to engage young people, thanks In the mid-18th century thousands of Museum houses the internationally into practice. and health – including its advances, to a Wellcome Trust Pulse award. unwanted children were left to die on important Foundling Hospital •‘Imagining the Future’, held at the decisions, dilemmas and impacts. Graham Mitchell’s Signs of Life, the streets of London. In 1719, after Collection, which includes paintings Theatre Royal Plymouth in February The PMS aims to encourage medical which explored people’s responses a life spent as a successful ship-builder by Hogarth, Gainsborough, Hudson 2003, brought together playwrights, students to see patients as individuals In 2004, the Eden Project received to genetic modification, was developed and sailor in the New World, retired sea and Roubilliac, and material relating theatre practitioners and scientists in particular social and cultural contexts. a £734 000 Rediscover award from in collaboration with students on captain Thomas Coram tripped over to Handel. for a week-long workshop. At least The arts and humanities – including the Millennium Commission and the a foundation degree course in one such baby left in a gutter. two new works emerged from the poetry writing, life-drawing, sculpture Wellcome Trust to redevelop its performance at Truro College. The Wellcome Trust provided funds workshop – Simon Turley’s Seeing and photography – are an important exhibition space. To engage visitors, Accompanied by associated role-play Stunned by the appalling social for an exhibition on the life and welfare Without Light, about immunity and part of this programme. the exhibits have the air of a fairground workshops, it toured secondary conditions all around him, he spent of these unfortunate youngsters. the impact of HIV, and Peter Morgan’s attraction with extensive use of automata schools in the south-west, and from the rest of his life establishing a refuge The Museum includes many objects Special, which explored the medical Among its many innovations, the and arcade game style exhibits. July 2004 was performed to school for abandoned children. His efforts reflecting the social and personal and cultural history of eugenics. PMS teaches anatomy without using All, however, illuminate the connections groups and the general public at were rewarded in 1739, when George history of its children, including cadavers, relying on imaging and between people and plants, wild places Eden’s Visitor Centre. II granted a Royal Charter for the hundreds of personal mementos • The Theatre Royal Plymouth went examination of living bodies instead. and cultures, across the globe. establishment of a Foundling Hospital, or ‘tokens’ left by mothers in the hope on to apply for a £250 000 Society Medical students first experience The Rediscover initiative was a £33 million joint to provide a home and education for that they might one day be able Award to build on the success of venture between the Millennium Commission, patients as living people rather than as But the Rediscover award is only the Wellcome Trust and the Wolfson Foundation. young children. to return and identify their child. these two plays. The theatre will work devitalised corpses. Similarly, the course one way in which the Eden Project These tokens, including a hazelnut with professional casts and local is case-based and students encounter has attempted to use innovative Coram solicited the help of a talented shell, a label from an ale bottle, community groups to develop the patients in normal settings, from set of friends. Handel wrote the and pieces of ribbon, are poignant plays and educational projects. hospitals to family planning clinics. hospital anthem; Hogarth contributed reminders of past anguish. paintings, and persuaded many • A reading of Peter Morgan’s play took Drama and role play form a key part of his contemporaries, including The Foundling Museum, at 40 Brunswick Square, place at the EuroScience Open Forum London WC1N 1AZ, is open Tuesday – Sunday, of students’ training, and drama Gainsborough and Reynolds, to 10.00–18.00. (Stockholm, August 2004). The play performances are even being taken do likewise. At that time there were deals with Sweden’s policy of into local schools to encourage students compulsory sterilisation of the

to consider a career in medicine. L to R ‘mentally defective’ – which only The medical school also draws upon Teaching anatomy ‘March of the guards ceased in the 1970s. The reading historical contexts, collaborating with without cadavers at to Finchley’, one of was followed by a discussion involving the historians at the University of Exeter, the Peninsula Medical Hogarth’s contributions the author and artist and commentator School. to the Foundling Hospital. a group supported by a Wellcome Eva Dahlgren, who has written The biomes of the Eden History of Medicine Strategy Award. Project in Cornwall. extensively about the Swedish policy. PUBLIC ENGAGEMENT PUBLIC ENGAGEMENT 32 33 MEDICAL PARADISE GAINS FOUNDLING FATHER A DRAMATIC INNOVATION YEAR Art is well known to benefit from Cornwall’s Eden Project aims to combine science, art and drama A new exhibition provides an insight into the lives of abandoned science. Less well appreciated to create a rich sensory experience for its visitors. children in the eighteenth century. is that science can gain from art.

UK science of academic science publishing. the UK population. The study was Physiological Sciences; Molecules, former Chief Executive of the Independent except for Wellcome Library personnel, We worked closely with the UK The research suggested that open carried out by an independent working Genes and Cells; and Medical Television Commission; Ronald Plasterk, who have moved to 210 Euston Road Government in the run-up to the launch access publishing was economically party chaired by Professor Stephen Humanities. These streams are Professor of Developmental Genetics while the Wellcome Trust’s previous of its ten-year framework for Science viable and offered the potential for Frankel, Professor of Epidemiology and complemented by ‘cross-cutting’ strands at the University of Utrecht; and Peter headquarters building at 183 Euston and Innovation. We welcomed the significant cost savings. Public Health at the University of Bristol. of activity such as technology transfer Smith, Professor of Tropical Epidemiology Road is refurbished. The refurbished Government’s decision to increase The group’s report, Public Health and public engagement. The aim of the at the London School of Hygiene and 183 building will be opened as a public framework spending from £3.9 billion Human Tissue Bill Sciences: Challenges and Opportunities, reorganisation is to focus more strongly Tropical Medicine. venue in 2006. in 2004 to £5 billion in 2008. During the year, we liaised with legislators addresses a major issue identified in the on research priorities and strategy, rather We have agreed to work jointly with and other parties to address issues raised recent Treasury-led Wanless Report, than on the funding process. Funding Sir David Steel New corporate identity the Government in key areas, such by the draft Human Tissue Bill, which in which recommended that the NHS should Committees and Strategy Committees Sir David Steel, former Chairman of the A new logo and corporate identity were as international health and public health its original form would have posed serious focus more on health improvement and are being set up to assess grants and Wellcome Trust, died on 9 August 2004. launched during the year. The new in the UK. We were also pleased to note problems to medical research in the UK. disease prevention rather than just consider strategy issues in each area. Sir David, previously Chairman of BP, identity, launched to coincide with the the Government’s acknowledgement The Human Tissue Bill was a response treatment of ill-health. was the Wellcome Trust’s Chairman occupation of the new headquarters of the contribution made by charities to cases in which the organs of deceased Flexible funding from 1982 to 1989. building, is being rolled out gradually. to research in UK higher education children were taken and stored without Consultation submissions In 2004, we made a number of changes The new identity is also reflected in the institutes, and its decision to provide the consent or knowledge of parents During the year, we submitted 27 formal to our grants management processes, New staff Wellcome Trust website, which was additional funds through the dual or families. While supportive of the aims responses to consultations launched with the aim of providing greater flexibility Four new senior members of staff were relaunched in 2004 in a more user- support system. of the bill, we and others feared that in by the UK Government and other bodies, for grantholders and reducing appointed during the year: Dr Ken Arnold, friendly format. its original form it could have put major including the draft charities bill, the Ten- administrative burdens for grantholders, Head of Public Programmes; Dr David Open access obstacles in the way of potentially life- Year Science and Innovation Investment universities and the Trust. The changes Lynn, Head of Strategic Planning and We have continued to promote the ‘open saving research. The revised bill Framework and the Scientific allow grantholders to move funds Policy; Frances Norton, Head of the access’ model of science publishing, addressed many of the medical research Publications Inquiry. between budget headings (except Wellcome Library; and Dr Jimmy to help ensure that scientific research community’s concerns, while still providing salary costs), and grants now include Whitworth, Head of International Activities. findings are shared as widely and as important protection to individuals’ rights. Streams a ‘flexible funding award’ to provide for rapidly as possible. In April 2004, we In October 2004, we introduced a unanticipated direct costs and to provide New headquarters published the findings of research carried Public health research funding ‘streams’ model for our research additional flexibility to researchers. The Wellcome Trust moved into new out by the consultants SQW, Costs and A working group commissioned by the funding activities. The new streams cover: purpose-built accommodation, the Gibbs Business Models in Scientific Research Wellcome Trust called for a national Immunology and Infectious Disease; New Governors Building at 215 Euston Road, during Publishing, which analysed the economic strategy to foster and enhance research Populations and Public Health; Three new Governors were appointed 2004. The new building brings together consequences of different models into major public health problems facing Neuroscience and Mental Health; in 2003/04: Dame Patricia Hodgson, all Wellcome Trust staff under one roof,

L to R The Gibbs Building – Heatherwick Studio, new headquarters in the Gibbs Building. of the Wellcome Trust. Dorsal root ganglion Colour-enhanced nerve cells. electron micrograph Frances Norton, who of the norovirus. joined the Trust as Head Detail of a spectacular of the Wellcome Library sculpture by the Thomas in July 2004. A YEAR AT THE WELLCOME TRUST A YEAR AT THE WELLCOME TRUST 34 35 A YEAR AT THE WELLCOME TRUST A brief overview of corporate activities in 2003/04.

L to R The Gibbs Building – Heatherwick Studio, new headquarters in the Gibbs Building. of the Wellcome Trust. Dorsal root ganglion Colour-enhanced nerve cells. electron micrograph Frances Norton, who of the norovirus. joined the Trust as Head Detail of a spectacular of the Wellcome Library sculpture by the Thomas in July 2004. FINANCIAL SUMMARY THE FUNDING YEAR 36 37 FINANCIAL SUMMARY THE FUNDING YEAR 1 October 2003 to 30 September 2004 A summary of major awards and key Wellcome Trust expenditure for 2003/04.

Grants awarded: £251 million Charitable resources expended (£ million) Breakdown of grants awarded (£ million)* in South-east Asia (Thailand and Vietnam), Public Engagement Kenya, Malawi and South Africa. The Public engagement funding is primarily £86 million Direct activities: Malawi programme received a £2.3 million through the Engaging Science Applications: 2988; 1141 awards grant, to enable it to continue its research programme. Rediscover funding – on malaria and other infections. a partnership with the Millennium Total charitable expenditure: £378 million Commission and the Wolfson Foundation Investment assets: £10.5 billion A £1.86 million grant was awarded – has enabled public venues such as the (as at 30 September 2004) Grants awarded 251 UK funding 101.4† to support research on women’s health Eden Project in Cornwall and ThinkTank Direct activities 86 Careers 70.2 and ageing populations in Lebanon in Birmingham to update exhibits. Support and administration costs 41 International 38.8 and elsewhere in the Middle East. Four 28.4‡ awards totalling £3.8 million were made A £10 million award to the Natural History Total charitable expenditure 378 Infrastructure and equipment Additional financial information can be found Medicine, Society and History 11.9 to countries in Latin and Central America Museum, for phase 2 of its Darwin in the Wellcome Trust’s Annual Report and – Brazil (two awards), Costa Rica and the Project, was confirmed. A £4.2 million Financial Statements 2004. Total 250.7 West Indies. award was made to the White Rose Consortium (an alliance between the In the year to 30 September 2004, Expenditure on direct activities, those * An additional £76.6 million was awarded to The Wellcome Trust supports research In 2003/04, 12 International Senior universities of Leeds, Sheffield and York), the Wellcome Trust’s total charitable organised by the Wellcome Trust, rose Wellcome Trust subsidiaries, mainly to support and other activities in four main areas: Research Fellowships were awarded to support construction of the National activities at the Wellcome Trust Sanger Institute. expenditure was £378 million. This slightly to £86 million. The bulk of these (seven in India, four in central/eastern Science Learning Centre at York. † Including £86.9 million awarded through the UK • Biomedical Science represents a drop on the figure for costs were for research at the Wellcome Europe, and one in South Africa); ten Subject Panels; £12.4 million awarded through • Technology Transfer 2002/03 (£516 million), due primarily Trust Sanger Institute, which received the Functional Genomics Development Initiative. were renewed (eight in India, one Direct activities to the decline in infrastructure funding £64 million in grants in 2003/04. Also ‡ Includes £14.2 million of capital awards in Medicine, • Medical Humanities in central/ eastern Europe, and one As well as funding others, the Wellcome through the Joint Infrastructure Fund included is £11 million committed to Society and History. • Public Engagement with Science in South Africa). Trust organises activities directly, either and Science Research Investment Fund the Diamond synchrotron project at the independently or in partnership with Grants paid and outstanding as these initiatives drew to a close. Chilton/Harwell Science Campus. Direct (£ million) In biomedical science, project and Technology Transfer others. The Wellcome Trust Sanger activity costs also include support for the programme support continued to This year was the first in which awards Institute accounted for £64 million for 118 5 116 8 Of the total charitable expenditure, grants Wellcome Library. account for the bulk of the Wellcome were made through the Wellcome Trust’s its ongoing highly productive research 1093 worth £251 million were awarded. 1028 Trust’s support in the UK. Research is new technology transfer schemes. programmes in genome sequencing Although grants expenditure was down Administration and support costs fell 979 primarily funded through response-mode University Translation Awards provide and analysis. on last year, the number of grant again, from £44 million to £41 million. mechanisms, with support provided for support for early-stage development applications received also decreased Wellcome Trust subsidiaries such investigator-led proposals in almost all of promising lines of research. The 16 Partnerships lay at the heart of several significantly – from 4312 in 2002/03 as the Genome Campus accounted areas of biomedical science and for a awards made this year covered a range public engagement projects, including to 2988, a drop of 30 per cent. for £6.7 million of this expenditure. wide range of basic and applied studies. of areas, including therapeutics, vaccines, the Imagine photographic competition Outstanding grant commitments again The following pages describe some of diagnostics and medical devices. run with the BBC, and the Pain exhibition shrank slightly this year, but remain Investments the major projects funded in 2003/04. at the Science Museum. in excess of £1 billion. The Wellcome Trust’s investments Strategic Translation Awards are large are managed to preserve (at least) the 412 391 Career development support is provided awards in areas of strategic importance Looking forward As in previous years, the bulk of grant purchasing power of its long-term asset 327 at all levels from PhD (through Four-year to the Trust. Four awards are currently In October 2004, the Wellcome Trust 274 support was for investigator-led base and to provide an income stream 223 PhD Programmes) to professorial-level at advanced stages of consideration. introduced a ‘streams’ model of funding. proposals in biomedical science. to support ongoing activities. This year, Principal Research Fellowships. The This is intended to provide a greater Fellowships and other careers funding the Trust’s asset base increased from 12 UK Four-year PhD Programmes all Medical Humanities focus on the needs and opportunities also continued to be a major area of £10.1 billion to £10.5 billion. received five-year renewals during the In the history of medicine, the year’s within particular areas. support (27.5 per cent of grants spend). 2000 2001 2002 2003 2004 year. Eight new Senior Research sole Strategic Award went to the International expenditure (funding Grants awarded (£ million) Fellowships were awarded (six Basic University of Oxford, for a programme Funding Committees and Strategy Grants paid for schemes focused on the needs 480 Biomedical Science and two Clinical of work on the history of tropical disease Committees are being established of developing and restructuring countries) Outstanding grant commitments Science), and eight fellowships were and medicine. Twentieth-century history to assess grant applications and increased as a proportion of total spend 41 9 renewed. Three Principal Research continued to provide a major focus, with to consider how the Trust might best (15.5 per cent of grants spend). 388 395 Grants awarded (left) represent the total funds committed Fellowships were renewed. topics being studied ranging from Unani make an impact in these areas. to successful applications during the Trust’s financial year. Most awards are made to researchers’ host practice in India to the history of Future Annual Reviews will report Grants for the medical humanities (history institutions, which then claim monies from the Trust. Infrastructure investment has returned myxomatosis in the UK. on the progress made by the streams of medicine and biomedical ethics) and The light purple in the figure above (grants paid) to levels seen before the surge of in funding and developing strategy. 2 5 1 public engagement with science represents the amounts claimed by host institutions spending through the Joint Infrastructure Funding continued for Biomedical amounted to £26.1 million. This consists during the year for expenses incurred, while the dark Fund and Science Research Investment Ethics studies, in the UK and the purple (outstanding grant commitments) represents of £11.9 million for response-mode the total sums committed by the Trust to projects which Fund. Funding of £11 million was developing world. Studies supported funding (2002/03: £13 million) plus capital had not been claimed by the end of the financial year. approved for phase 2 of the Diamond are of practical relevance, including the awards to the Natural History Museum The gap between committed funds and cash paid is synchrotron project. function of clinical ethics committees and due to the long-term nature of many grants, and to the (£10 million) and for the National Science time lag between a grant award and the subsequent an assessment of the impact of research Learning Centre (£4.2 million). 2000 2001 2002 2003 2004 claim for funds from an institution. The Wellcome Trust’s international on health policy makers in Kenya. The Diamond funding is primarily focused on regional synchrotron, which received a funding centres of excellence, particularly boost in 2004. IMMUNOLOGY AND INFECTIOUS DISEASE IMMUNOLOGY AND INFECTIOUS DISEASE 38 39 IMMUNOLOGY AND INFECTIOUS DISEASE The Immunology and Infectious Disease stream aims to increase our knowledge and understanding of the infectious organisms that cause disease in humans and animals, and of the immune system that fights these organisms. During the year, 70 immunology and immune system of healthy but infected The Wellcome Trust Centre infectious disease awards were made, persons, but in immunocompromised for Molecular Parasitology including 15 new programme grants individuals it presents a major clinical or renewals, to a total value of problem. Using clinical isolates, The Wellcome Trust Centre for Molecular £26.6 million. Dr Wilkinson will look at how the virus Parasitology at the University of Glasgow, interacts with natural killer cells, the led by Professor Dave Barry, carries out Research funded in the immunology main weapon in fighting viral disease. research on basic features of parasites, and infectious disease area ranged The team will use whole genome using genetic and molecular technology from fundamental and applied research cloning techniques to investigate the allied with organismal biology. One aim in basic immunology and infectious role of different viral genes in evading is that such studies will lead to novel diseases conducted in the UK through these immune cells. control approaches. to field, epidemiological and clinical research based in developing countries. • Professor David Wraith, University Much of the research at the Centre of Bristol, for research on the concerns African trypanosomes, Professor Brian Spratt, Imperial College, differentiation and stability of induced microscopic parasites that cause human had the programme grant associated with regulatory T cells. Professor Wraith’s of neonatal healthcare locally, attracting • Analysis of data on the spectrum and clinical evidence from the research sleeping sickness and the wasting his Principal Research Fellowship renewed research is aimed at the development the interest of the Ministry of Health and of bacteraemia in children, with data publications of the programme have disease nagana in domestic animals. at a cost of £1.7 million. Professor Spratt, of therapies to control autoimmune other NGOs/charities (see page 27). from over 20 000 children admitted provided a basis for a change in global The malaria parasite, Plasmodium, who has been a Principal Research Fellow conditions, such as multiple sclerosis. to hospital. Of all hospital deaths, antimalarial treatment and a related parasite, Theileria, which since 1989, studies the epidemiology and Major Overseas Programmes 14 per cent were attributable to recommendations to artemisinin infects cells of the cattle immune system, evolution of bacterial populations, and has Under the Tropical Medicine Following a favourable review in 2004, Streptococcus pneumoniae and combination therapies (ACTs) are also studied at the Centre. pioneered the use of multi-locus Programme, awards included a Senior an award of £2.3 million was made Haemophilus influenzae, for which (see page 24). sequence typing as a scientific and Clinical Fellowship in Tropical Medicine to the University of Liverpool for the effective vaccines are available but In 2004, the Centre established a new epidemiological tool. to Dr Elizabeth Corbett, London School Malawi–Liverpool–Wellcome Trust only partially implemented. • A mathematical–economic model partnership with INSERM, the national of Hygiene and Tropical Medicine, for Clinical Research Programme. The of drug resistance has been used medical research agency of the French Senior Research Fellowships in Basic trials of TB case-finding strategies in an programme, which is led by Professor • Dr Sam Kinyanjui and Dr Faith Osier as a basis for the global Government. INSERM has begun to Biomedical Science were awarded to urban community in Zimbabwe severely Malcolm Molyneux and is based in the were awarded Research Training recommendations on antimalarial locate its researchers in universities Dr Allison Green, University of Cambridge, affected by HIV, and a Career Wellcome Trust Research Laboratories Fellowships for Scientists from drug policy issued in a recent abroad, and the first of these INSERM for studies into inflammation and Development Fellowship to Dr Cameron at the University of Malawi College of Developing Countries to conduct Institute of Medicine report (Saving Research Units, led by Professor autoimmune disease, and to Dr Daniel Simmons, University of Oxford, for his Medicine, Blantyre, conducts research research at the KEMRI–Wellcome Lives, Buying Time). Christian Doerig, has been established van Aalten, University of Dundee, for studies in Vietnam on cellular immune into malaria, HIV, TB and other bacterial Trust programme in Kilifi. at the Centre. his studies on structural biology and response and disease pathogenesis and viral infections, and anaemia. • In Vietnam, the Programme has inhibitor design in chitin metabolism. during dengue infection. Dr Corbett In addition to research costs, the award In South-east Asia, which completed the largest-ever study During the year, a programme grant was awarded the 2004 Chalmers medal provides funds to support the training encompasses research centres in of TB meningitis (see page 26). was awarded to Professor Andy Tait Fifteen programme grants were awarded, by the Royal Society of Tropical Medicine of local researchers associated with the Thailand (led by Professor Nick Day) at the Centre, based on his application including grants to: and Hygiene for her contributions to programme (see page 25). and Vietnam (Professor Jeremy Farrar), • The Vietnam Programme has been of genetics to the identification of tropical medicine. research highlights include: at the forefront of the battle against important trypanosome genes. Professor • Professor Jose Vazquez-Boland, who In Kenya building work began on new the outbreak of avian flu (see Tait’s mapping and annotation of the moved from the University of Leon in An interim review was carried out of the laboratories in Kilifi for the Wellcome • Demonstration that variable horizontal page 23). trypanosome genome has been Spain to take up the Chair of Veterinary Wellcome Trust/Burroughs Wellcome Trust/Kenya Medical Research Institute gene acquisition by Burkholderia invaluable to the genome sequencing Molecular Microbiology at the University Fund Infectious Diseases Initiative. Research Programme, led by Professor pseudomallei is an important feature • The New Adult Intensive Care work on the parasite being carried out of Bristol, for his studies of the Launched in 1999, the initiative awarded Kevin Marsh. The building has been of its recent genetic evolution. Unit at the Hospital for Tropical at the Wellcome Trust Sanger Institute molecular and cellular pathogenesis of £18 million to support 13 projects, each funded by a Wellcome Trust grant of Diseases opened in 2004, funded and elsewhere. Listeria infection. Listeriosis has one of involving partners in the UK, USA and a £2.75 million to the Kenya Medical • Continued translation of the jointly by the Vietnamese Government the highest hospitalisation and mortality developing country, and has played an Research Institute. The building should Programme’s research results into and the Wellcome Trust. www.gla.ac.uk/centres/wcmp/index.html rates of all food-borne infections. important role in fostering international be completed by August 2005. health policy. Biological, economic Professor Vazquez-Boland is partnerships and developing capacity. investigating the actin-based Research highlights from the Kenya mechanism of cell–cell spread used While many projects have yet to come programme include: by the bacterium. to full fruition, it is clear that they have delivered major benefits to the participants • The completion of a survey of epilepsy • Dr Gavin Wilkinson, University of Wales and host institutions, and in some cases in over 160 000 people and the College of Medicine, Cardiff, for studies have had a direct impact on public identification of all cases of active into human cytomegalovirus. This health. For example, the project based epilepsy, the largest study of its kind herpesvirus is able to evade the in Bangladesh has raised the profile ever conducted in Africa.

Adenovirus particles. IMMUNOLOGY AND INFECTIOUS DISEASE IMMUNOLOGY AND INFECTIOUS DISEASE 38 39 IMMUNOLOGY AND INFECTIOUS DISEASE The Immunology and Infectious Disease stream aims to increase our knowledge and understanding of the infectious organisms that cause disease in humans and animals, and of the immune system that fights these organisms. During the year, 70 immunology and immune system of healthy but infected The Wellcome Trust Centre infectious disease awards were made, persons, but in immunocompromised for Molecular Parasitology including 15 new programme grants individuals it presents a major clinical or renewals, to a total value of problem. Using clinical isolates, The Wellcome Trust Centre for Molecular £26.6 million. Dr Wilkinson will look at how the virus Parasitology at the University of Glasgow, interacts with natural killer cells, the led by Professor Dave Barry, carries out Research funded in the immunology main weapon in fighting viral disease. research on basic features of parasites, and infectious disease area ranged The team will use whole genome using genetic and molecular technology from fundamental and applied research cloning techniques to investigate the allied with organismal biology. One aim in basic immunology and infectious role of different viral genes in evading is that such studies will lead to novel diseases conducted in the UK through these immune cells. control approaches. to field, epidemiological and clinical research based in developing countries. • Professor David Wraith, University Much of the research at the Centre of Bristol, for research on the concerns African trypanosomes, Professor Brian Spratt, Imperial College, differentiation and stability of induced microscopic parasites that cause human had the programme grant associated with regulatory T cells. Professor Wraith’s of neonatal healthcare locally, attracting • Analysis of data on the spectrum and clinical evidence from the research sleeping sickness and the wasting his Principal Research Fellowship renewed research is aimed at the development the interest of the Ministry of Health and of bacteraemia in children, with data publications of the programme have disease nagana in domestic animals. at a cost of £1.7 million. Professor Spratt, of therapies to control autoimmune other NGOs/charities (see page 27). from over 20 000 children admitted provided a basis for a change in global The malaria parasite, Plasmodium, who has been a Principal Research Fellow conditions, such as multiple sclerosis. to hospital. Of all hospital deaths, antimalarial treatment and a related parasite, Theileria, which since 1989, studies the epidemiology and Major Overseas Programmes 14 per cent were attributable to recommendations to artemisinin infects cells of the cattle immune system, evolution of bacterial populations, and has Under the Tropical Medicine Following a favourable review in 2004, Streptococcus pneumoniae and combination therapies (ACTs) are also studied at the Centre. pioneered the use of multi-locus Programme, awards included a Senior an award of £2.3 million was made Haemophilus influenzae, for which (see page 24). sequence typing as a scientific and Clinical Fellowship in Tropical Medicine to the University of Liverpool for the effective vaccines are available but In 2004, the Centre established a new epidemiological tool. to Dr Elizabeth Corbett, London School Malawi–Liverpool–Wellcome Trust only partially implemented. • A mathematical–economic model partnership with INSERM, the national of Hygiene and Tropical Medicine, for Clinical Research Programme. The of drug resistance has been used medical research agency of the French Senior Research Fellowships in Basic trials of TB case-finding strategies in an programme, which is led by Professor • Dr Sam Kinyanjui and Dr Faith Osier as a basis for the global Government. INSERM has begun to Biomedical Science were awarded to urban community in Zimbabwe severely Malcolm Molyneux and is based in the were awarded Research Training recommendations on antimalarial locate its researchers in universities Dr Allison Green, University of Cambridge, affected by HIV, and a Career Wellcome Trust Research Laboratories Fellowships for Scientists from drug policy issued in a recent abroad, and the first of these INSERM for studies into inflammation and Development Fellowship to Dr Cameron at the University of Malawi College of Developing Countries to conduct Institute of Medicine report (Saving Research Units, led by Professor autoimmune disease, and to Dr Daniel Simmons, University of Oxford, for his Medicine, Blantyre, conducts research research at the KEMRI–Wellcome Lives, Buying Time). Christian Doerig, has been established van Aalten, University of Dundee, for studies in Vietnam on cellular immune into malaria, HIV, TB and other bacterial Trust programme in Kilifi. at the Centre. his studies on structural biology and response and disease pathogenesis and viral infections, and anaemia. • In Vietnam, the Programme has inhibitor design in chitin metabolism. during dengue infection. Dr Corbett In addition to research costs, the award In South-east Asia, which completed the largest-ever study During the year, a programme grant was awarded the 2004 Chalmers medal provides funds to support the training encompasses research centres in of TB meningitis (see page 26). was awarded to Professor Andy Tait Fifteen programme grants were awarded, by the Royal Society of Tropical Medicine of local researchers associated with the Thailand (led by Professor Nick Day) at the Centre, based on his application including grants to: and Hygiene for her contributions to programme (see page 25). and Vietnam (Professor Jeremy Farrar), • The Vietnam Programme has been of genetics to the identification of tropical medicine. research highlights include: at the forefront of the battle against important trypanosome genes. Professor • Professor Jose Vazquez-Boland, who In Kenya building work began on new the outbreak of avian flu (see Tait’s mapping and annotation of the moved from the University of Leon in An interim review was carried out of the laboratories in Kilifi for the Wellcome • Demonstration that variable horizontal page 23). trypanosome genome has been Spain to take up the Chair of Veterinary Wellcome Trust/Burroughs Wellcome Trust/Kenya Medical Research Institute gene acquisition by Burkholderia invaluable to the genome sequencing Molecular Microbiology at the University Fund Infectious Diseases Initiative. Research Programme, led by Professor pseudomallei is an important feature • The New Adult Intensive Care work on the parasite being carried out of Bristol, for his studies of the Launched in 1999, the initiative awarded Kevin Marsh. The building has been of its recent genetic evolution. Unit at the Hospital for Tropical at the Wellcome Trust Sanger Institute molecular and cellular pathogenesis of £18 million to support 13 projects, each funded by a Wellcome Trust grant of Diseases opened in 2004, funded and elsewhere. Listeria infection. Listeriosis has one of involving partners in the UK, USA and a £2.75 million to the Kenya Medical • Continued translation of the jointly by the Vietnamese Government the highest hospitalisation and mortality developing country, and has played an Research Institute. The building should Programme’s research results into and the Wellcome Trust. www.gla.ac.uk/centres/wcmp/index.html rates of all food-borne infections. important role in fostering international be completed by August 2005. health policy. Biological, economic Professor Vazquez-Boland is partnerships and developing capacity. investigating the actin-based Research highlights from the Kenya mechanism of cell–cell spread used While many projects have yet to come programme include: by the bacterium. to full fruition, it is clear that they have delivered major benefits to the participants • The completion of a survey of epilepsy • Dr Gavin Wilkinson, University of Wales and host institutions, and in some cases in over 160 000 people and the College of Medicine, Cardiff, for studies have had a direct impact on public identification of all cases of active into human cytomegalovirus. This health. For example, the project based epilepsy, the largest study of its kind herpesvirus is able to evade the in Bangladesh has raised the profile ever conducted in Africa.

Adenovirus particles. MOLECULES, GENES AND CELLS MOLECULES, GENES AND CELLS 40 41 MOLECULES, GENES AND CELLS The Molecules, Genes and Cells stream aims to support high-quality research that will further our understanding of the fundamental molecular, cellular and genetic processes involved in health and disease.

During the year, 75 awards Wellcome Trust Centre susceptibility; and understanding of Life Sciences at the University cell responses to fluid shear stress). were made, including nine new for Cell Biology how gene variants contribute to risk of Manchester. Its long-term aims are A programme grant was awarded programme grants or renewals, of disease in the population and how to elucidate the structure and function to Professor Neil Bulleid (see left). to a total value of £21.8 million. The Wellcome Trust Centre for Cell genetic factors contribute biologically of the extracellular matrix (ECM) and Two Principal Research Fellowships Biology at the University of Edinburgh, to a disease process. cell–matrix adhesions, define the www.wtccmr.man.ac.uk were renewed: to Professor Angus led by Professor Adrian Bird, seeks contribution of cell–matrix interactions Lamond (University of Dundee), to understand the fundamental The Centre, located in the Henry to human diseases, and develop Wellcome Trust/Cancer Research for his structural and functional characteristics of living things at the Wellcome Building of Genomic Medicine, approaches for preventing and treating UK Gurdon Institute analysis of the mammalian cell cellular level, such as growth, movement, houses multidisciplinary research teams these diseases. nucleus, and to Professor Bill self-replication and development. in human genetics, functional genomics, The Wellcome Trust/Cancer Research Earnshaw (University of Edinburgh) bioinformatics, statistical genetics and Research within the Centre is organised UK Gurdon Institute of Cancer and for his studies of non-histone It has particular strengths in the study structural biology. The Centre is focusing as four integrated programmes: Developmental Biology at the University chromosomal proteins in mitosis of RNA, including its transcription, on three main disease areas in its genetics (1) molecular basis and cellular control of Cambridge, chaired by Professor and apoptosis. processing, transport and destruction; research programme: neurogenetics, of ECM assembly, (2) organisation Jim Smith, focuses on two inter-related the cell division cycle; and gene genetics of inflammation and immunity, of signalling at the cell–ECM interface, aspects of cell biology: how cells acquire Membrane trafficking and protein to study protein folding and misfolding expression in developing systems, and the genetics of cardiovascular (3) microenvironmental determination and maintain their normal function during folding were notable themes in this using an array of biophysical particularly epigenetic processes such disease/metabolic syndrome. of cell fate, and (4) cell–ECM engineering development, and how they escape from year’s molecular and cell biology techniques and theoretical simulations. as DNA methylation. and tissue regeneration. While each normal controls and become cancerous. funding. Professor Margaret Robinson A Senior Research Fellowship in Clinical programme is highly focused on (University of Cambridge) had the Several important and innovative During the year Professor Bill Earnshaw’s Science was awarded to Dr Julian Knight extracellular matrices and cell–matrix The Institute adopted its new name programme grant associated with grants were also funded in the area Principal Research Fellowship was (Characterisation of genetic variation interactions, the long-term promise during the year, in recognition of the her Principal Research Fellowship of epigenetics and gene silencing. renewed (see left), as was Dr Kenneth regulating gene expression within the of the work overlaps with some of the pioneering scientific contributions made on coated vesicle adaptors renewed. Jane Mellor (University of Oxford) was Sawin’s Senior Research Fellowship MHC class III region). A Senior Research most important areas of biomedical by its founding Director, Sir John Gurdon. She is characterising the adaptor awarded a programme grant to in Basic Biomedical Science (Regulation Fellowship in Basic Biomedical Science research – signalling, tissue engineering Sir John was also awarded the Royal protein complexes that facilitate elucidate the role of a novel chromatin of eukaryotic microtubule nucleation was renewed: Dr Dominique Gauguier and medical genetics. Society’s Copley Medal, its top honour. the transport of cargo between remodelling ATPase in gene silencing and microtubule-mediated cell polarity). (Functional genomics of type 2 diabetes intracellular organelles. A new line and gene regulation. A Research Career Development quantitative trait loci in rat models). In 2001, the University of Manchester In 2004, the Institute also occupied its of investigation will focus on how the Fellowship was awarded to Dr Maria A Research Career Development was awarded £15 million from the Joint new building, constructed with support human immunodeficiency virus (HIV) Professor Constanze Bonifer (University Vogelauer (see left). Fellowship was awarded to Dr Richard Infrastructure Fund (JIF) to help set up from the Joint Infrastructure Fund. may exploit adaptor proteins to evade of Leeds) received continued project Wade-Martins (Functional analysis a new Integrative Centre for Molecular the immune response. grant funding for her studies on the Professor David Tollervey, a Wellcome of the tau genomic locus and its role Cell Biology. An additional £35 million from www.gurdon.cam.ac.uk epigenetic mechanisms regulating the Principal Research Fellow at the Centre, in neurodegeneration). the university was used to create a large Professor Colin Stirling (University expression of the lysozyme gene, while was elected to the Royal Society, while research facility for biomedical research • Research resources: see page 19 of Manchester) received continued Dr Brian Hendrich (University of Professor Jean Beggs was awarded Dr Kalim Mir, a Wellcome Career sited at a central location in the programme grant funding for studies Edinburgh) was awarded a grant, the Royal Society Darwin Trust Development Fellow, received a university’s biomedical corridor, adjacent of protein biogenesis in the yeast complementing his ongoing Wellcome Research Professorship. Technology Development Grant (Ultra- to the Manchester Royal Infirmary and endoplasmic reticulum. By using both fellowship support, to investigate the throughput parallel DNA sequencing using the Wellcome Trust Clinical Research the powerful genetic systems of yeast epigenetic silencing mechanisms in cell www.wcb.ed.ac.uk/intro.htm a heuristic single molecule array strategy). Facility. This building, named in honour and biochemical approaches, his fate decisions. Dr Maria Vogelauer Researchers at the Centre also received of Professor Michael Smith, was occupied group will investigate the partitioning received a Research Career • RNA-based gene silencing: see page 19 two clinical training fellowships. in 2004 and now houses the Wellcome of proteins into the secretory pathway Development Fellowship to study the Trust Centre for Cell-Matrix Research. via the endoplasmic reticulum and molecular mechanisms by which Wellcome Trust Centre www.well.ox.ac.uk the role of the translocon complex histone acetylation regulates the timing for Human Genetics During the year a Senior Research and associated chaperones. of replication origin firing. • Population genetic structure: see page 6 Fellowship in Basic Biomedical Science The Wellcome Trust Centre for Human was awarded to Richard Kammerer Professor Neil Bulleid (University Biological chemistry Genetics at the University of Oxford, Wellcome Trust Centre (Elucidating the mechanisms of of Manchester) was awarded a The partnership with the Royal Society led by Professor Tony Monaco, studies for Cell-Matrix Research angiopoietin function and amyloid programme grant to continue of Chemistry to encourage the area the mechanisms controlling genetic formation by protein engineering and his studies on oxidative folding of chemical biology continued during susceptibility to human disease. This The Wellcome Trust Centre for Cell- de novo design). A Research Career in the mammalian endoplasmic the year. A successful workshop on includes the localisation and identification Matrix Research, led by Professor Martin Development Fellowship was awarded reticulum. His group studies the redox ‘Chemistry at the Biological Interface’ of disease genes; functional analysis of Humphries, is an interdisciplinary research to Dr Eleni Tzima (Role of cell–cell conditions within the endoplasmic was held at the University of Warwick gene variants responsible for centre embedded within the Faculty junctions and integrins in endothelial reticulum that allow proteins, particularly in September 2004. The participants, those containing disulphide bonds, from universities in and around the to fold correctly. Midlands, enthusiastically discussed collaborative projects and it is likely that Professor Christopher Dobson several new grants will be submitted (University of Cambridge) received from ideas first aired at the workshop. continued programme grant funding Normal red blood cells. NEUROSCIENCE AND MENTAL HEALTH PHYSIOLOGICAL SCIENCES 42 43 NEUROSCIENCE AND PHYSIOLOGICAL MENTAL HEALTH SCIENCES The Neuroscience and Mental Health stream aims to support high-quality The Physiological Sciences stream aims to support high-quality basic and clinical research into the function of the nervous system in health and disease. research relevant to the understanding of biological processes at the cell, organ, system and whole-animal level in health and disease. During the year, 63 physiological his studies into the physiology and sciences awards were made, including pathophysiology of beta-cell exocytosis seven new programme grants or and insulin secretion. Greater insight into renewals, to a total value of the control of insulin secretion has the £20.2 million. potential to inform both our fundamental knowledge of the defects involved in Physiological science awards covered type 2 diabetes and the development a broad range of basic and clinical of novel therapies to treat this debilitating research. Awards were made in areas and widespread condition. This award as diverse as epidemiology – for was of further importance as it aided example, to Dr Louise Parker (University the recruitment and retention of of Newcastle), for an analysis of a historical Professor Rorsman, an internationally birth cohort to explore the effect of pre- renowned scientist previously working and post-natal exposure to airborne outside the UK. particulate matter on subsequent During the year, 62 neuroscience factors in infancy affect the occurrence Furthering our understanding of how mortality and health – and organ In this same general theme, an award arrhythmia in the heart. These tools awards were made, including 11 of psychiatric disorders during the key these molecules enable neurons to transplantation – such as the award was made to Professor David Dunger will be accessible on the web for other new programme grants or renewals, changes accompanying adolescence. communicate is important in their further to Professor Peter Friend (University and colleagues (University of Cambridge) investigators to use in further studies. to a total value of £26.6 million. His group will be carrying out a development as targets for drugs for of Oxford), for the development of a for a study looking at the effect of genetic One Principal Research Fellowship longitudinal study of 13 and 14 year-olds diseases of the nervous system. novel preservation technique for donor variation in the insulin gene on birth Another award for multidisciplinary was renewed, to Professor Chris Frith to find associations of selected genes livers involving warm perfusion. weight and perinatal survival in African research was made to Dr David Webb (Institute of Neurology) for his studies and childhood adversity with depression A number of projects are aiming to clarify populations. This study will, for the first (Aston University) and colleagues at of social interactions (see page 8). and associated conditions. how the very complex connections in One notable theme during the year time, test the hypothesis that genes the University of Birmingham. They are the nervous system develop. Dr Uwe centred on appetite control, nutrition relating to size at birth influence fetal developing a ‘smart vest’ which, when Neuroscience awards continued to cover Several awards were for basic research Drescher (King’s College London), for and body size, obesity and their and postnatal survival. worn next to the skin, will collect clinically a wide range of both basic and clinical projects aiming to increase our knowledge example, is examining how neurons can impact on health, particularly diabetes. useful information related to respiration. research topics throughout 2003/04. of how neurons communicate with be directed to their targets, which are Awards included a programme grant A significant amount of multidisciplinary Such information should aid clinicians Two examples of the diversity of funding each other – essential for our often a great distance away, by guidance to Professor Stephen Bloom (Imperial research was also funded through the in the diagnosis of respiratory disease. are awards to Dr Lucia Sivilotti (University understanding of the nervous system. molecules. Dr Drescher is studying the College London) for his studies aimed year. This included an award to Professor College London), for a highly detailed Two awards were made to groups at differential expression of genes at critical at exploiting the discovery that gut David Paterson and colleagues at the As well as grant funding, a joint MRC/ study of the subunits of the nicotinic University College London, to Professors times of development which assist in hormones physiologically control Universities of Oxford and Auckland (New Wellcome Trust workshop was organised acetylcholine receptor, and Dr Marianne David Attwell and Stuart Cull-Candy. guiding neuronal projections from the appetite. This programme will examine Zealand) for a heart ‘physiome’ project. on integrative physiology. The workshop, van den Bree (University of Wales, Professor Attwell’s group will be involved retina to the tectum. how different gut hormones produce The aim of their project is to demonstrate held in May 2004, brought together basic Cardiff) who is carrying out a longitudinal in studies into how neurotransmitters their effects and interact in obese and the use of integrative multi-scale modelling and clinical physiologists and explored study in adolescents of the risk factors function in ways distinct from Professor Kristjan Jessen (University lean volunteers. The research should – at the levels of atoms, proteins, cells, how an appropriate strategy to further associated with substance abuse. conventional fast synaptic transmission College London) was awarded a grant provide a better understanding of the tissues and organs – to relate detailed encourage integrative physiology might between neurons, looking particularly to study the development of Schwann complex interactions in appetite genomic information to a model of the be developed. Two significant awards were made at their communication with glia cells. cells within the nervous system. These regulation and provide new strategies structure and function of the human heart. in the field of child psychiatry. The first Professor Cull-Candy’s research will very specialised cells form the myelin to treat and prevent obesity. Since biological systems are extremely was to Professor Alan Stein (University examine how changes in receptor sheath which insulates nerve axons complex, the team will develop specially of Oxford) for his ongoing work which subunits define the nature of and are essential for normal nerve Another significant award in a related designed instrumentation, databases aims to understand how maternal neurotransmission at glutamate function. However, following injury they area was made to Professor Patrik and software to help understand the postnatal psychiatric disorders can affect and GABA synapses. can revert to an immature state, leading Rorsman (University of Oxford), for genetic basis of mechanisms underlying the development of a child, even after to demyelination of the axon and loss the mother has recovered. His group Other research projects are looking of function. Professor Jessen’s group will be looking at how interactions at chemicals that are not classical is examining the signals that control between mother and child are affected neurotransmitters but have a major role Schwann cell differentiation and the by postnatal depression, following infants in neuronal transmission. One such process of myelination, and will also in the first years of life to see how they award was made to Professor Alan look at mechanisms that may allow subsequently develop. North (University of Manchester), who the Schwann cells to form new myelin is studying the role of ATP, classically sheaths and thus aid nerve repair In a related study, Professor Ian Goodyer known as a molecule which transfers following injury. (University of Cambridge) will be looking energy within cells, which interacts at how genetic and environmental risk with specific receptors on neurons. L to R Neurons in the brain.

Professors David Paterson (left) and Peter Hunter of the Heart Physiome Project. NEUROSCIENCE AND MENTAL HEALTH PHYSIOLOGICAL SCIENCES 42 43 NEUROSCIENCE AND PHYSIOLOGICAL MENTAL HEALTH SCIENCES The Neuroscience and Mental Health stream aims to support high-quality The Physiological Sciences stream aims to support high-quality basic and clinical research into the function of the nervous system in health and disease. research relevant to the understanding of biological processes at the cell, organ, system and whole-animal level in health and disease. During the year, 63 physiological his studies into the physiology and sciences awards were made, including pathophysiology of beta-cell exocytosis seven new programme grants or and insulin secretion. Greater insight into renewals, to a total value of the control of insulin secretion has the £20.2 million. potential to inform both our fundamental knowledge of the defects involved in Physiological science awards covered type 2 diabetes and the development a broad range of basic and clinical of novel therapies to treat this debilitating research. Awards were made in areas and widespread condition. This award as diverse as epidemiology – for was of further importance as it aided example, to Dr Louise Parker (University the recruitment and retention of of Newcastle), for an analysis of a historical Professor Rorsman, an internationally birth cohort to explore the effect of pre- renowned scientist previously working and post-natal exposure to airborne outside the UK. particulate matter on subsequent During the year, 62 neuroscience factors in infancy affect the occurrence Furthering our understanding of how mortality and health – and organ In this same general theme, an award arrhythmia in the heart. These tools awards were made, including 11 of psychiatric disorders during the key these molecules enable neurons to transplantation – such as the award was made to Professor David Dunger will be accessible on the web for other new programme grants or renewals, changes accompanying adolescence. communicate is important in their further to Professor Peter Friend (University and colleagues (University of Cambridge) investigators to use in further studies. to a total value of £26.6 million. His group will be carrying out a development as targets for drugs for of Oxford), for the development of a for a study looking at the effect of genetic One Principal Research Fellowship longitudinal study of 13 and 14 year-olds diseases of the nervous system. novel preservation technique for donor variation in the insulin gene on birth Another award for multidisciplinary was renewed, to Professor Chris Frith to find associations of selected genes livers involving warm perfusion. weight and perinatal survival in African research was made to Dr David Webb (Institute of Neurology) for his studies and childhood adversity with depression A number of projects are aiming to clarify populations. This study will, for the first (Aston University) and colleagues at of social interactions (see page 8). and associated conditions. how the very complex connections in One notable theme during the year time, test the hypothesis that genes the University of Birmingham. They are the nervous system develop. Dr Uwe centred on appetite control, nutrition relating to size at birth influence fetal developing a ‘smart vest’ which, when Neuroscience awards continued to cover Several awards were for basic research Drescher (King’s College London), for and body size, obesity and their and postnatal survival. worn next to the skin, will collect clinically a wide range of both basic and clinical projects aiming to increase our knowledge example, is examining how neurons can impact on health, particularly diabetes. useful information related to respiration. research topics throughout 2003/04. of how neurons communicate with be directed to their targets, which are Awards included a programme grant A significant amount of multidisciplinary Such information should aid clinicians Two examples of the diversity of funding each other – essential for our often a great distance away, by guidance to Professor Stephen Bloom (Imperial research was also funded through the in the diagnosis of respiratory disease. are awards to Dr Lucia Sivilotti (University understanding of the nervous system. molecules. Dr Drescher is studying the College London) for his studies aimed year. This included an award to Professor College London), for a highly detailed Two awards were made to groups at differential expression of genes at critical at exploiting the discovery that gut David Paterson and colleagues at the As well as grant funding, a joint MRC/ study of the subunits of the nicotinic University College London, to Professors times of development which assist in hormones physiologically control Universities of Oxford and Auckland (New Wellcome Trust workshop was organised acetylcholine receptor, and Dr Marianne David Attwell and Stuart Cull-Candy. guiding neuronal projections from the appetite. This programme will examine Zealand) for a heart ‘physiome’ project. on integrative physiology. The workshop, van den Bree (University of Wales, Professor Attwell’s group will be involved retina to the tectum. how different gut hormones produce The aim of their project is to demonstrate held in May 2004, brought together basic Cardiff) who is carrying out a longitudinal in studies into how neurotransmitters their effects and interact in obese and the use of integrative multi-scale modelling and clinical physiologists and explored study in adolescents of the risk factors function in ways distinct from Professor Kristjan Jessen (University lean volunteers. The research should – at the levels of atoms, proteins, cells, how an appropriate strategy to further associated with substance abuse. conventional fast synaptic transmission College London) was awarded a grant provide a better understanding of the tissues and organs – to relate detailed encourage integrative physiology might between neurons, looking particularly to study the development of Schwann complex interactions in appetite genomic information to a model of the be developed. Two significant awards were made at their communication with glia cells. cells within the nervous system. These regulation and provide new strategies structure and function of the human heart. in the field of child psychiatry. The first Professor Cull-Candy’s research will very specialised cells form the myelin to treat and prevent obesity. Since biological systems are extremely was to Professor Alan Stein (University examine how changes in receptor sheath which insulates nerve axons complex, the team will develop specially of Oxford) for his ongoing work which subunits define the nature of and are essential for normal nerve Another significant award in a related designed instrumentation, databases aims to understand how maternal neurotransmission at glutamate function. However, following injury they area was made to Professor Patrik and software to help understand the postnatal psychiatric disorders can affect and GABA synapses. can revert to an immature state, leading Rorsman (University of Oxford), for genetic basis of mechanisms underlying the development of a child, even after to demyelination of the axon and loss the mother has recovered. His group Other research projects are looking of function. Professor Jessen’s group will be looking at how interactions at chemicals that are not classical is examining the signals that control between mother and child are affected neurotransmitters but have a major role Schwann cell differentiation and the by postnatal depression, following infants in neuronal transmission. One such process of myelination, and will also in the first years of life to see how they award was made to Professor Alan look at mechanisms that may allow subsequently develop. North (University of Manchester), who the Schwann cells to form new myelin is studying the role of ATP, classically sheaths and thus aid nerve repair In a related study, Professor Ian Goodyer known as a molecule which transfers following injury. (University of Cambridge) will be looking energy within cells, which interacts at how genetic and environmental risk with specific receptors on neurons. L to R Neurons in the brain.

Professors David Paterson (left) and Peter Hunter of the Heart Physiome Project. POPULATIONS AND PUBLIC HEALTH MEDICAL HUMANITIES 44 45 POPULATIONS AND MEDICAL HUMANITIES PUBLIC HEALTH The Medical Humanities stream aims to enhance understanding of the historical and social context of medicine and biomedical science. It supports research The Populations and Public Health stream aims to improve our understanding programmes in history of medicine and biomedical ethics, and encourages of the determinants of disease and quality of life in populations. It promotes use of research findings, for example to inform public policy making. the use of this understanding to improve public health and healthcare delivery. During the year, 53 awards were made University of KwaZulu-Natal, South Africa In the history of medicine, a Strategic Wellcome Trust Centre for the in this area, principally through the has been awarded funding for a feasibility Award was made to Dr Mark Harrison History of Medicine Health Consequences of Population study to examine different approaches (University of Oxford) for his study Change Programme, to a total value to using antiretroviral drugs against HIV ‘The history of infectious disease, and Research at the The Wellcome Trust of £12.7 million. infections in resource-poor settings. medicine in the tropics’. Enhancement Centre for the History of Medicine at These drugs are normally used on a long- Awards were made to Professor University College London, led by Latin America term basis to suppress disease, with Virginia Berridge (London School Professor Hal Cook, spans a wide An initiative to support Centres of careful monitoring of patients – presenting of Hygiene and Tropical Medicine), range of topics, eras and countries. Excellence in Latin America culminated major challenges where the numbers of Professor Anne Crowther (University The Centre also organises outreach in the award of four programmes (totalling people in need are large and resources of Glasgow) and Dr Nick Hopwood activities and teaching at undergraduate, £3.8 million) to support multidisciplinary are scarce. (University of Cambridge). Master’s and PhD levels. The Centre research on the impact on health began a new MA course in 2004, of demographic and socioeconomic The Trust-funded building housing the Two University Awards were made, recruiting 13 students from a variety changes in the region. Professor Mauricio Africa Centre at Somkhele has been to Dr Tim McHugh (Oxford Brookes of backgrounds. Barreto (Univesidade da Bahia, Salvador, widely praised – a tribute to a distinctive University; Rural medical charity and Brazil) will study the impact of building that reflects the Centre’s and Tropical Medicine, with the University society in Brittany, 1598–1789) and in 2003/04, primarily project grants Professor Janet Browne continued to urbanisation, migration and lifestyle commitment to community-based health of Chile) will be evaluating a nutritional Dr Rosemary Elliot (University of but including six fellowships, nine add to the prizes awarded to her book changes on allergic diseases (atopy research. A series of regional and national supplementation and exercise programme Glasgow; Smoking and health in studentships and 17 symposia. Charles Darwin: Volume 2 – The power and asthma). A parallel study in Quito, awards culminated in the South African initiated by the Government of Chile. Germany from occupation to The Wellcome Trust also organised of place (Jonathan Cape), including the Ecuador, in collaboration with Dr Philip Institute of Architects Award of Excellence reunification, 1945–1995). Fellowship a workshop, ‘Investigating ethics W H Heinemann prize from The Royal Cooper (a Wellcome Trust Senior for 2002, where the building was Professor Astrid Fletcher (London School and project support covered a wide and mental disorders’. Society of Literature. Her book was also Research Fellow), will compare the described as one of the best ever built of Hygiene and Tropical Medicine, with range of topics, from Unani practice short-listed for the British Academy Book prevalence of allergic diseases, and risk in South Africa. the All India Institute of Medical Sciences) in India to fungal diseases in Among the research projects funded, Prize 2003. factors, in rural and urban populations. will continue research into age-related modern medicine. Dr Sheila McLean (University of Professor Huda Zurayk, Center for eye disease in India, following a Glasgow) was awarded a project grant Professor Vivian Nutton’s Ancient Also in Brazil, Professor Cesar Victora Research in Population and Health, successful Trust-funded pilot study. Preservation to review and evaluate clinical ethics Medicine was published by Routledge (Federal University of Pelotas) will American University of Beirut, was This is a population-based study to map The Research Resources in Medical committees in the UK. Dr Robin in 2004, while six Wellcome Witnesses compare two large birth cohorts to awarded a £1.86 million programme grant prevalence rates for macular degeneration History scheme was set up to improve Williams (University of Durham) received to Twentieth Century Medicine, published explore how early life factors – such as to continue her studies on reproductive and cataract, the impact of these access to documentary collections that project grant funding for follow-up to his by the Centre, are now available online. nutrition, socioeconomic, cultural and health of women, health of adolescents conditions on quality of life, and possible are important to historians of medicine, previous study on the UK National DNA healthcare issues – influence adolescent and the elderly in the Middle East. risk factors such as diet, smoking and use by funding preservation, conservation, database, this time reviewing forensic The Centre has a varied outreach and adult health. The award reflects the progress made of cooking fuels. cataloguing and digitisation projects. databasing in support of criminal programme. Professor Roger Cooter since it was awarded a ‘regional centre investigation in the EU states, and how began a column in the Lancet on Professor Luis Rosero-Bixby’s team of excellence’ grant in 2001. UK Biobank In June 2004, the scheme was DNA data are being shared across ‘Keywords in the history of medicine’, (Universidad de Costa Rica) will address The UK Biobank project, a partnership extended for a further two years, with national borders. while members of the Centre appeared the role of social, nutritional and Training between the Wellcome Trust, the Medical funds of £500 000 available each year. in the six-part Radio 4 programme The healthcare factors in longevity and active The Master’s-level Research Training Research Council and the Department In its first four years, the scheme has Dr Mike English, a clinician at the Other Medicine presented by Anna Ford. life expectancy in the country, while Fellowship scheme was reviewed during of Health, will collect current health, funded 58 projects to a total value of KEMRI/Wellcome Trust Major Overseas Dr Sanjoy Bhattacharya and Dr Andrew collaborations with Cuba and Mexico the year. The awards consist of a taught lifestyle and medical history data on £2 million. Programme in Kenya, was awarded Hull advised and appeared on the recent will study how different public health course, followed by a research project 500 000 volunteers aged 40–69. The data project grant support to investigate Channel 4 documentary The Great Asian approaches affect ageing in the region. in the applicant’s home country. In all, will be a powerful tool for researchers An evaluation of the scheme carried out the research-to-policy-to-practice Invasion discussing the role of Asian 67 individuals received Masters’ support exploring the origins of complex diseases. in 2004 discovered that institutions that pathway in Kenya. He will explore doctors in the formation of the NHS. Finally, Dr Elsie Le Franc (University of the between 1998 and 2002. Most have In November 2003, UK Biobank Ltd was have received funding for cataloguing the environment in which health policy Professor Kan-wen Ma contributed West Indies) will examine the possible thrived professionally and still appear established as a charitable company and now urgently require second-stage decisions are made, mapping out the to parliamentary consultations on the causes of family and interpersonal to be working in their home country, in January 2004 the Board of Directors, funding for preservation and linkages and information flow between regulation of complementary and violence, especially among adolescents attesting to the success of the scheme chaired by Sir Alan Langlands, Principal conservation. As a result, the new key stakeholder groups. alternative medicine. and young adults. The project will assess in strengthening research capacity. and Vice-Chancellor of the University scheme is focusing primarily on a number of possible risk factors, of Dundee, held its first full meeting. preservation and conservation, although The development of novel diagnostics, www.ucl.ac.uk/histmed including family structure, social networks, Other notable awards In August 2004, Alastair Campbell, proposals for cataloguing projects will therapeutics and health services is and instabilities resulting from migration. Two awards under the Health Professor of Ethics in Medicine at the still be accepted. increasingly predicated on the search Consequences of Population Change University of Bristol’s School of Medicine, for significant biological differences Major centres Programme address key areas in ageing was appointed chair of the UK Biobank Biomedical ethics within and between populations. Dr Michael Bennish at the Africa Centre research – diet and vision. Professor Ethics and Governance Council. Research is supported on issues Dr Paul Martin (University of Nottingham) for Health and Population Studies, Ricardo Uauy (London School of Hygiene relevant to policy and practice in the UK was funded to investigate how the and the conduct of biomedical research categories of race/ethnicity are used L to R in the developing world. A total of 50 in research and what their practical awards in biomedical ethics were made impact might be. Boys in Kenya. Dr Mark Harrison of the University of Oxford. POPULATIONS AND PUBLIC HEALTH MEDICAL HUMANITIES 44 45 POPULATIONS AND MEDICAL HUMANITIES PUBLIC HEALTH The Medical Humanities stream aims to enhance understanding of the historical and social context of medicine and biomedical science. It supports research The Populations and Public Health stream aims to improve our understanding programmes in history of medicine and biomedical ethics, and encourages of the determinants of disease and quality of life in populations. It promotes use of research findings, for example to inform public policy making. the use of this understanding to improve public health and healthcare delivery. During the year, 53 awards were made University of KwaZulu-Natal, South Africa In the history of medicine, a Strategic Wellcome Trust Centre for the in this area, principally through the has been awarded funding for a feasibility Award was made to Dr Mark Harrison History of Medicine Health Consequences of Population study to examine different approaches (University of Oxford) for his study Change Programme, to a total value to using antiretroviral drugs against HIV ‘The history of infectious disease, and Research at the The Wellcome Trust of £12.7 million. infections in resource-poor settings. medicine in the tropics’. Enhancement Centre for the History of Medicine at These drugs are normally used on a long- Awards were made to Professor University College London, led by Latin America term basis to suppress disease, with Virginia Berridge (London School Professor Hal Cook, spans a wide An initiative to support Centres of careful monitoring of patients – presenting of Hygiene and Tropical Medicine), range of topics, eras and countries. Excellence in Latin America culminated major challenges where the numbers of Professor Anne Crowther (University The Centre also organises outreach in the award of four programmes (totalling people in need are large and resources of Glasgow) and Dr Nick Hopwood activities and teaching at undergraduate, £3.8 million) to support multidisciplinary are scarce. (University of Cambridge). Master’s and PhD levels. The Centre research on the impact on health began a new MA course in 2004, of demographic and socioeconomic The Trust-funded building housing the Two University Awards were made, recruiting 13 students from a variety changes in the region. Professor Mauricio Africa Centre at Somkhele has been to Dr Tim McHugh (Oxford Brookes of backgrounds. Barreto (Univesidade da Bahia, Salvador, widely praised – a tribute to a distinctive University; Rural medical charity and Brazil) will study the impact of building that reflects the Centre’s and Tropical Medicine, with the University society in Brittany, 1598–1789) and in 2003/04, primarily project grants Professor Janet Browne continued to urbanisation, migration and lifestyle commitment to community-based health of Chile) will be evaluating a nutritional Dr Rosemary Elliot (University of but including six fellowships, nine add to the prizes awarded to her book changes on allergic diseases (atopy research. A series of regional and national supplementation and exercise programme Glasgow; Smoking and health in studentships and 17 symposia. Charles Darwin: Volume 2 – The power and asthma). A parallel study in Quito, awards culminated in the South African initiated by the Government of Chile. Germany from occupation to The Wellcome Trust also organised of place (Jonathan Cape), including the Ecuador, in collaboration with Dr Philip Institute of Architects Award of Excellence reunification, 1945–1995). Fellowship a workshop, ‘Investigating ethics W H Heinemann prize from The Royal Cooper (a Wellcome Trust Senior for 2002, where the building was Professor Astrid Fletcher (London School and project support covered a wide and mental disorders’. Society of Literature. Her book was also Research Fellow), will compare the described as one of the best ever built of Hygiene and Tropical Medicine, with range of topics, from Unani practice short-listed for the British Academy Book prevalence of allergic diseases, and risk in South Africa. the All India Institute of Medical Sciences) in India to fungal diseases in Among the research projects funded, Prize 2003. factors, in rural and urban populations. will continue research into age-related modern medicine. Dr Sheila McLean (University of Professor Huda Zurayk, Center for eye disease in India, following a Glasgow) was awarded a project grant Professor Vivian Nutton’s Ancient Also in Brazil, Professor Cesar Victora Research in Population and Health, successful Trust-funded pilot study. Preservation to review and evaluate clinical ethics Medicine was published by Routledge (Federal University of Pelotas) will American University of Beirut, was This is a population-based study to map The Research Resources in Medical committees in the UK. Dr Robin in 2004, while six Wellcome Witnesses compare two large birth cohorts to awarded a £1.86 million programme grant prevalence rates for macular degeneration History scheme was set up to improve Williams (University of Durham) received to Twentieth Century Medicine, published explore how early life factors – such as to continue her studies on reproductive and cataract, the impact of these access to documentary collections that project grant funding for follow-up to his by the Centre, are now available online. nutrition, socioeconomic, cultural and health of women, health of adolescents conditions on quality of life, and possible are important to historians of medicine, previous study on the UK National DNA healthcare issues – influence adolescent and the elderly in the Middle East. risk factors such as diet, smoking and use by funding preservation, conservation, database, this time reviewing forensic The Centre has a varied outreach and adult health. The award reflects the progress made of cooking fuels. cataloguing and digitisation projects. databasing in support of criminal programme. Professor Roger Cooter since it was awarded a ‘regional centre investigation in the EU states, and how began a column in the Lancet on Professor Luis Rosero-Bixby’s team of excellence’ grant in 2001. UK Biobank In June 2004, the scheme was DNA data are being shared across ‘Keywords in the history of medicine’, (Universidad de Costa Rica) will address The UK Biobank project, a partnership extended for a further two years, with national borders. while members of the Centre appeared the role of social, nutritional and Training between the Wellcome Trust, the Medical funds of £500 000 available each year. in the six-part Radio 4 programme The healthcare factors in longevity and active The Master’s-level Research Training Research Council and the Department In its first four years, the scheme has Dr Mike English, a clinician at the Other Medicine presented by Anna Ford. life expectancy in the country, while Fellowship scheme was reviewed during of Health, will collect current health, funded 58 projects to a total value of KEMRI/Wellcome Trust Major Overseas Dr Sanjoy Bhattacharya and Dr Andrew collaborations with Cuba and Mexico the year. The awards consist of a taught lifestyle and medical history data on £2 million. Programme in Kenya, was awarded Hull advised and appeared on the recent will study how different public health course, followed by a research project 500 000 volunteers aged 40–69. The data project grant support to investigate Channel 4 documentary The Great Asian approaches affect ageing in the region. in the applicant’s home country. In all, will be a powerful tool for researchers An evaluation of the scheme carried out the research-to-policy-to-practice Invasion discussing the role of Asian 67 individuals received Masters’ support exploring the origins of complex diseases. in 2004 discovered that institutions that pathway in Kenya. He will explore doctors in the formation of the NHS. Finally, Dr Elsie Le Franc (University of the between 1998 and 2002. Most have In November 2003, UK Biobank Ltd was have received funding for cataloguing the environment in which health policy Professor Kan-wen Ma contributed West Indies) will examine the possible thrived professionally and still appear established as a charitable company and now urgently require second-stage decisions are made, mapping out the to parliamentary consultations on the causes of family and interpersonal to be working in their home country, in January 2004 the Board of Directors, funding for preservation and linkages and information flow between regulation of complementary and violence, especially among adolescents attesting to the success of the scheme chaired by Sir Alan Langlands, Principal conservation. As a result, the new key stakeholder groups. alternative medicine. and young adults. The project will assess in strengthening research capacity. and Vice-Chancellor of the University scheme is focusing primarily on a number of possible risk factors, of Dundee, held its first full meeting. preservation and conservation, although The development of novel diagnostics, www.ucl.ac.uk/histmed including family structure, social networks, Other notable awards In August 2004, Alastair Campbell, proposals for cataloguing projects will therapeutics and health services is and instabilities resulting from migration. Two awards under the Health Professor of Ethics in Medicine at the still be accepted. increasingly predicated on the search Consequences of Population Change University of Bristol’s School of Medicine, for significant biological differences Major centres Programme address key areas in ageing was appointed chair of the UK Biobank Biomedical ethics within and between populations. Dr Michael Bennish at the Africa Centre research – diet and vision. Professor Ethics and Governance Council. Research is supported on issues Dr Paul Martin (University of Nottingham) for Health and Population Studies, Ricardo Uauy (London School of Hygiene relevant to policy and practice in the UK was funded to investigate how the and the conduct of biomedical research categories of race/ethnicity are used L to R in the developing world. A total of 50 in research and what their practical awards in biomedical ethics were made impact might be. Boys in Kenya. Dr Mark Harrison of the University of Oxford. TECHNOLOGY TRANSFER WELLCOME TRUST GENOME CAMPUS 46 47 TECHNOLOGY TRANSFER WELLCOME TRUST GENOME CAMPUS Technology Transfer at the Wellcome Trust seeks to maximise the impact of research The Wellcome Trust Genome Campus, at Hinxton, near Cambridge, is home to the innovations on health by facilitating the development of early-stage projects to a point Wellcome Trust Sanger Institute, the Wellcome Trust Conference Centre and Wellcome at which they can be further developed by the market. Trust Advanced Courses. The Genome Campus is currently being extended to provide additional laboratory and ancillary space.

too early to appreciate the full impact These may be technologies that have the zebrafish genome was a priority, Medicine) and Genomes 2004 (with of the funding provided. a particular role in support of the Trust’s but there was an increasing emphasis The Institute for Genomic Research mission and address an unmet need on re-sequencing in humans, mice and Institut Pasteur). In March 2003 the Wellcome Trust in healthcare, and where Technology and pathogens to document variation announced two new forms of translation Transfer can add value by providing and identify disease-causing alleles. These events have been well attended award. University Translation Awards project management support or securing and well received, and more will be provide a response-mode funding stream. follow-on funding. In the past year the Sanger Institute has organised for 2004/05 and beyond. As such, they are used to support a identified genes that play a role in diverse array of technologies, not only Four Strategic Translation Award diabetes and lung cancer (see pages Wellcome Trust Advanced Courses from biology but also from the physical applications have been considered since 12, 22), while the genome of MRSA The Wellcome Trust Advanced Courses sciences and mathematics. The common the scheme was announced. These (methicillin-resistant Staphylococcus programme provides postdoctoral requirements are that the research is related to diagnostics, vaccination and a aureus) was decoded. The Sanger researchers with hands-on training aimed at the improvement of health and novel genotyping technology. The mean Institute plays a leading role in identifying in emerging research techniques. that the project can be advanced to a value of the awards was £1.3 million. variation in the major histocompatibility The courses, which are attended by point at which it represents an attractive Further developments in strategically complex – a key part of the immune researchers from all over the world, For the Wellcome Trust to achieve its proposition for follow-on support by a important translational research are likely Wellcome Trust Sanger Institute system which is also involved in are held in dedicated laboratories in mission, it is important that the basic third party. Both academic institutions to be announced in the coming year. The Wellcome Trust Sanger Institute autoimmune diseases such as arthritis the Wellcome Trust Sanger Institute. discoveries made by the scientific and associated early-stage companies is one of the world’s leading scientific and type 1 diabetes. community are translated into practical are eligible to apply for these translation There has been encouraging progress establishments, generating and providing During the year four Advanced Courses innovations that can be utilised directly awards. Managing projects to a successful in a number of the projects supported data and resources to the global scientific Teams from the Sanger Institute have were held – Genotype to Protein, DNA or indirectly to improve human and outcome is the responsibility of the through the Development Fund. CellTran, community. Genome sequence and the been funded by the US National Institutes Microarrays, Functional Genomics and animal health. To be effective in institution or company management. a spin-out company from the University multitude of variants present in a of Health to contribute to the ENCODE Human Genome Analysis. In addition four translating scientific advances into of Sheffield, launched a ‘smart bandage’ population are responsible for many (Encyclopedia of DNA Elements) project, bioinformatics Open Door Workshops health products, scientists need Technology Transfer has just completed product called ‘Myskin’ for the treatment of the differences between individuals, a consortium that aims to put in place the were held, giving participants hands-on to engage with the business and the first full year of funding of University of serious burns (see page 27). Another from cognition to cancer predisposition best technologies to map all functional experience of working with human and investment community. Bridging the Translation Awards. Of 58 applications early-stage company, Diagnostics for in humans to virulence in pathogens. elements of the genome. In its initial pilot pathogen genome sequences. gap between academic research and received from 30 institutions, 25 per cent the Real World, has developed dipstick Hence DNA sequence provides an phase, 1 per cent of the human genome commercial R&D is difficult because were awarded. An equivalent number of technology for the diagnosis of Chlamydia essential platform for much of is being evaluated. The Advanced Courses programme of the risks inherent to early-stage awards were made to university infection (see page 22). biomedical research. was positively reviewed in 2003, translation. This is a particular problem departments and small businesses. The Sanger Institute now has established and new courses will be added from in the healthcare sector, where the The mean value of these awards was The year also saw important develop- The Sanger Institute produced the largest major activities in mouse genetics and 2004/05 onwards in key areas. technical and regulatory hurdles are £276 000 (range: £48 000 to £594 000). ments in a drug discovery project, based contribution to finished human genome this year announced the development a significant challenge on the path In keeping with the response-mode nature at the Institute of Cancer Research, on sequence (see page 6), and has also of SITGR and MICER, two resources for South Field Project to market. of the scheme, projects were funded that a mutant form of the B-Raf kinase developed tools such as the Ensembl mouse functional genomics. These freely The South Field Project, the £95 million addressed a wide range of potential associated with malignant melanoma. gene browser which enable hundreds available resources are dramatically development of the Genome Campus, Technology Transfer at the Wellcome applications – including therapeutics, The project is being taken forward by of thousands of researchers to view and accelerating the process of discovering remained on schedule to be completed Trust seeks to mitigate the risks of early- vaccines, diagnostics and medical a partnership that includes the Institute utilise genome sequence data from 17 gene function in mice in laboratories in 2005. stage translation by funding projects devices, as well as new platform itself, Cancer Research Technology, the different species via the web, with human across the globe. that are too early to attract venture capital technologies. One award was made Wellcome Trust Sanger Institute, the and mouse the most popular. The 13 000 square metre development or to be seen by industry as credible to investigate the effectiveness of policy Wellcome Trust and Astex Technology, Wellcome Trust Conference Centre will provide additional research in-licensing opportunities. Up to 2003, tools for promoting translation in a biotech company with expertise in drug In 2004, papers from the Sanger Institute The Conference Centre continued laboratories and data-handling it achieved this through the £20 million neglected diseases, such as malaria discovery, especially structure–activity describing the sequence content of to expand its activities, hosting some facilities for the Sanger Institute and Development Fund. Over a period of five and African sleeping sickness. relationship research. With the expanded chromosomes 6, 9 and 10 – a total 200 meetings and more than 7500 improved ancillary facilities for all years, this has supported around 40 team, the programme is set to progress of nearly 400 million base pairs – were delegates. Highlights of the year included Genome Campus staff. The laboratories projects from 14 institutions. Many of Strategic Translation Awards are through the critical phases of lead published. The Sanger Institute has now five large Wellcome Trust Conferences – will provide additional space for genomic these have raised additional investment a second form of funding designed selection and lead optimisation over produced some 2.5 billion base pairs Functional Genomics, Days of Molecular and molecular biology research, while the and two have developed products already to support translational research in areas the coming year. of finished sequence. Medicine, Genomes 2004, Functional data centre will provide a substantial (see pages 22 and 27), although it is still of key importance to the Wellcome Trust. Genomics of Host–Pathogen increase in the computing power of the The Sanger Institute has increased its Interactions, and Genome Informatics. Sanger Institute, making it one of the faculty strength to 35, as its programmes most advanced in Europe. The ancillary evolve to place a greater emphasis on The latter two events were held jointly building houses a new lecture room, gene function through genetic analysis with Cold Spring Harbor Laboratory. restaurant facilities and sports hall and in humans and model organisms. International collaboration was also gymnasium. Completion and handover of a feature of Days of Molecular Medicine the project is scheduled for spring 2005. High-volume sequencing continues to fuel (coorganised with the University L to R many of these activities: during last year of California San Diego and Nature Zebrafish embryos. Scientists at the Sanger Institute. TECHNOLOGY TRANSFER WELLCOME TRUST GENOME CAMPUS 46 47 TECHNOLOGY TRANSFER WELLCOME TRUST GENOME CAMPUS Technology Transfer at the Wellcome Trust seeks to maximise the impact of research The Wellcome Trust Genome Campus, at Hinxton, near Cambridge, is home to the innovations on health by facilitating the development of early-stage projects to a point Wellcome Trust Sanger Institute, the Wellcome Trust Conference Centre and Wellcome at which they can be further developed by the market. Trust Advanced Courses. The Genome Campus is currently being extended to provide additional laboratory and ancillary space. too early to appreciate the full impact These may be technologies that have the zebrafish genome was a priority, Medicine) and Genomes 2004 (with of the funding provided. a particular role in support of the Trust’s but there was an increasing emphasis The Institute for Genomic Research mission and address an unmet need on re-sequencing in humans, mice and Institut Pasteur). In March 2003 the Wellcome Trust in healthcare, and where Technology and pathogens to document variation announced two new forms of translation Transfer can add value by providing and identify disease-causing alleles. These events have been well attended award. University Translation Awards project management support or securing and well received, and more will be provide a response-mode funding stream. follow-on funding. In the past year the Sanger Institute has organised for 2004/05 and beyond. As such, they are used to support a identified genes that play a role in diverse array of technologies, not only Four Strategic Translation Award diabetes and lung cancer (see pages Wellcome Trust Advanced Courses from biology but also from the physical applications have been considered since 12, 22), while the genome of MRSA The Wellcome Trust Advanced Courses sciences and mathematics. The common the scheme was announced. These (methicillin-resistant Staphylococcus programme provides postdoctoral requirements are that the research is related to diagnostics, vaccination and a aureus) was decoded. The Sanger researchers with hands-on training aimed at the improvement of health and novel genotyping technology. The mean Institute plays a leading role in identifying in emerging research techniques. that the project can be advanced to a value of the awards was £1.3 million. variation in the major histocompatibility The courses, which are attended by point at which it represents an attractive Further developments in strategically complex – a key part of the immune researchers from all over the world, For the Wellcome Trust to achieve its proposition for follow-on support by a important translational research are likely Wellcome Trust Sanger Institute system which is also involved in are held in dedicated laboratories in mission, it is important that the basic third party. Both academic institutions to be announced in the coming year. The Wellcome Trust Sanger Institute autoimmune diseases such as arthritis the Wellcome Trust Sanger Institute. discoveries made by the scientific and associated early-stage companies is one of the world’s leading scientific and type 1 diabetes. community are translated into practical are eligible to apply for these translation There has been encouraging progress establishments, generating and providing During the year four Advanced Courses innovations that can be utilised directly awards. Managing projects to a successful in a number of the projects supported data and resources to the global scientific Teams from the Sanger Institute have were held – Genotype to Protein, DNA or indirectly to improve human and outcome is the responsibility of the through the Development Fund. CellTran, community. Genome sequence and the been funded by the US National Institutes Microarrays, Functional Genomics and animal health. To be effective in institution or company management. a spin-out company from the University multitude of variants present in a of Health to contribute to the ENCODE Human Genome Analysis. In addition four translating scientific advances into of Sheffield, launched a ‘smart bandage’ population are responsible for many (Encyclopedia of DNA Elements) project, bioinformatics Open Door Workshops health products, scientists need Technology Transfer has just completed product called ‘Myskin’ for the treatment of the differences between individuals, a consortium that aims to put in place the were held, giving participants hands-on to engage with the business and the first full year of funding of University of serious burns (see page 27). Another from cognition to cancer predisposition best technologies to map all functional experience of working with human and investment community. Bridging the Translation Awards. Of 58 applications early-stage company, Diagnostics for in humans to virulence in pathogens. elements of the genome. In its initial pilot pathogen genome sequences. gap between academic research and received from 30 institutions, 25 per cent the Real World, has developed dipstick Hence DNA sequence provides an phase, 1 per cent of the human genome commercial R&D is difficult because were awarded. An equivalent number of technology for the diagnosis of Chlamydia essential platform for much of is being evaluated. The Advanced Courses programme of the risks inherent to early-stage awards were made to university infection (see page 22). biomedical research. was positively reviewed in 2003, translation. This is a particular problem departments and small businesses. The Sanger Institute now has established and new courses will be added from in the healthcare sector, where the The mean value of these awards was The year also saw important develop- The Sanger Institute produced the largest major activities in mouse genetics and 2004/05 onwards in key areas. technical and regulatory hurdles are £276 000 (range: £48 000 to £594 000). ments in a drug discovery project, based contribution to finished human genome this year announced the development a significant challenge on the path In keeping with the response-mode nature at the Institute of Cancer Research, on sequence (see page 6), and has also of SITGR and MICER, two resources for South Field Project to market. of the scheme, projects were funded that a mutant form of the B-Raf kinase developed tools such as the Ensembl mouse functional genomics. These freely The South Field Project, the £95 million addressed a wide range of potential associated with malignant melanoma. gene browser which enable hundreds available resources are dramatically development of the Genome Campus, Technology Transfer at the Wellcome applications – including therapeutics, The project is being taken forward by of thousands of researchers to view and accelerating the process of discovering remained on schedule to be completed Trust seeks to mitigate the risks of early- vaccines, diagnostics and medical a partnership that includes the Institute utilise genome sequence data from 17 gene function in mice in laboratories in 2005. stage translation by funding projects devices, as well as new platform itself, Cancer Research Technology, the different species via the web, with human across the globe. that are too early to attract venture capital technologies. One award was made Wellcome Trust Sanger Institute, the and mouse the most popular. The 13 000 square metre development or to be seen by industry as credible to investigate the effectiveness of policy Wellcome Trust and Astex Technology, Wellcome Trust Conference Centre will provide additional research in-licensing opportunities. Up to 2003, tools for promoting translation in a biotech company with expertise in drug In 2004, papers from the Sanger Institute The Conference Centre continued laboratories and data-handling it achieved this through the £20 million neglected diseases, such as malaria discovery, especially structure–activity describing the sequence content of to expand its activities, hosting some facilities for the Sanger Institute and Development Fund. Over a period of five and African sleeping sickness. relationship research. With the expanded chromosomes 6, 9 and 10 – a total 200 meetings and more than 7500 improved ancillary facilities for all years, this has supported around 40 team, the programme is set to progress of nearly 400 million base pairs – were delegates. Highlights of the year included Genome Campus staff. The laboratories projects from 14 institutions. Many of Strategic Translation Awards are through the critical phases of lead published. The Sanger Institute has now five large Wellcome Trust Conferences – will provide additional space for genomic these have raised additional investment a second form of funding designed selection and lead optimisation over produced some 2.5 billion base pairs Functional Genomics, Days of Molecular and molecular biology research, while the and two have developed products already to support translational research in areas the coming year. of finished sequence. Medicine, Genomes 2004, Functional data centre will provide a substantial (see pages 22 and 27), although it is still of key importance to the Wellcome Trust. Genomics of Host–Pathogen increase in the computing power of the The Sanger Institute has increased its Interactions, and Genome Informatics. Sanger Institute, making it one of the faculty strength to 35, as its programmes most advanced in Europe. The ancillary evolve to place a greater emphasis on The latter two events were held jointly building houses a new lecture room, gene function through genetic analysis with Cold Spring Harbor Laboratory. restaurant facilities and sports hall and in humans and model organisms. International collaboration was also gymnasium. Completion and handover of a feature of Days of Molecular Medicine the project is scheduled for spring 2005. High-volume sequencing continues to fuel (coorganised with the University L to R many of these activities: during last year of California San Diego and Nature Zebrafish embryos. Scientists at the Sanger Institute. PUBLIC ENGAGEMENT PUBLIC ENGAGEMENT 48 49 PUBLIC ENGAGEMENT The Wellcome Trust’s Public Engagement activities aim to raise awareness and understanding of biomedical science, its social and ethical implications and its historical context.

of filmed interviews with scientific and Public participation The Wellcome Trust Gallery at the British implications of increased longevity, while subject. This enabled them to get first- medical professionals researching In September 2004 the Wellcome Trust Museum, funded by a £5.4 million grant Dying for change: Infectious disease hand experience of historically significant inherited genetic disorders, by artist and BBC Science launched the second to the British Museum, opened on in the developing world examined objects without needing to make a Jacqueline Donachie and geneticist Imagine photographic competition to 3 November 2003 with Living and Dying the reasons underlying the huge impact special trip. Dr Darren Monckton. encourage school groups, young people (see page 31). of infectious disease in resource- and adults to explore ‘how is science poor countries. The Wellcome Trust contributed A notable award under the Young changing us?’ Pharmakon ran from 17 October 2003 £750 000 to a project promoting open People’s theme was for a project at the to 6 February 2004 at the TwoTen Gallery Wellcome Library access to published scientific papers. University of Bristol, which will create The Wellcome Trust organised a series on Euston Road. The exhibition featured Significant progress was made on the Run by the Wellcome Library, the Joint young people’s Research Ethics of online debates and public events works from the US artist Beverly Fishman. cataloguing of the Wellcome Foundation Information Systems Committee and Committees. School students will with Spiked, an online publisher and Ltd archive (which was transferred to the the US National Library of Medicine, consider real grant applications and discussion forum (www.spiked- Wonderful: Visions of the near future, Wellcome Library from GlaxoSmithKline the new project will digitise the full text feed back comments to the actual online.com). The opening debate in the a major collaborative science and art in 2001). The cataloguing project will help of every issue of a number of important panels considering the applications. series, ‘Fearing the Unknown: Are we venture exploring the languages and illuminate both the early development medical journals. too risk averse?’ questioned whether assumptions of art and science and what of the Wellcome pharmaceutical Grants A total of 31 People Awards – a fast- society was excessively preoccupied happens when these research interests company and the wider history of the Publications A total of 41 Society Awards were response mechanism to support smaller with exaggerated risks. The second fuse, opened at the Arnolfini Gallery in pharmaceutical industry in the UK. Talking Heads: Cognitive behavioural awarded under the £3 million Engaging projects – were also funded under the debate, ‘Human Body Parts’, focused Bristol in February 2004. Supported by therapy comes of age, the latest Science grants programme. These large Engaging Science programme. on issues around the Human Tissue Bill, the Wellcome Trust and other partners, Public outreach, particularly with Wellcome News Supplement, was awards of £50 000 or more support including consent and the use of human Wonderful comprises a national touring schools and young people, was a feature published in June 2004. It featured public engagement projects in designated In 2003, 27 awards were made through tissue and organs in research. Debates exhibition, new commissions, live work, of the Wellcome Library’s year. Fourteen articles exploring the latest thinking areas – in 2003/04, ‘broadening access’, the Pulse initiative, which encouraged were also organised with the Institute an education CD-ROM, conference, students from South Camden Community on cognitive behavioural therapy – ‘young people’s education’ and ‘Sciart’. youth theatre and dance companies to of Contemporary Arts. The first publication and interpretative film. School, all refugees, embarked on the and how it is being applied to a wide develop new performance arts projects debate looked at privacy and questions Remedies and Recipes project. After range of disorders, including depression, Society Awards under the ‘broadening to engage young people with science. of how personal biomedical data Education visiting the Wellcome Library to examine social phobia, post-traumatic stress access’ theme included an award to The projects embraced a huge spectrum are used; the second at the pathway Construction work began on the new a range of recipe books they compiled disorder, schizophrenia and borderline Dr Guto Roberts to introduce biomedical of themes, including the bioscience from research to the media. National Science Learning Centre their own books of home cures from personality disorder. science to the National Eisteddfod of of light, neuroscience, cloning, eugenics, at the University of York, part of the both the UK and their home countries. Wales, the most important annual cultural ageing and vaccination programmes. Exhibitions £51 million national network of Science An evaluation of The Human Genome festival of Wales, and one to Dr Carolyn Pain: Passion, compassion, sensibility Learning Centres being funded by the Two GCSE Medicine Through Time microsite – which provides key Stephens at the London School of This year saw many performances ran from 13 February to 20 June 2004 Wellcome Trust and the Department INSET days were run by the Wellcome information about the human genome – Hygiene and Tropical Medicine, to see based on projects funded through Pulse. at the Medicine in Context Gallery at the for Education and Skills. The national Library in partnership with the Schools indicated that the site is a valuable and whether children’s participation in In addition, a two-day conference Science Museum (see page 30). To centre, which is due to open in autumn History Project (www.tasc.ac.uk/shp) with widely used resource; it attracted epidemiological research can stimulate at the University of Manchester (25–26 accompany the exhibition, a public event, 2005, will be run by the White Rose the aim of improving teachers’ knowledge around 280 000 visitors in the year. an interest in medical science. June 2004) featured performances and The Heartache of St Valentine's Day, was Consortium. The national network aims and increasing their confidence in A microsite was also developed to enabled participants to share thoughts held at the Dana Centre on 11 February to provide enhanced professional teaching the history of medicine. The accompany the Pain exhibition, Ten Research and Development Awards about their experiences. The initiative 2004, while a series of films and debates development opportunities for science first, held in January 2004, examined providing articles on the science, of up to £15 000 were awarded under has been so successful that a second about pain were organised at the Institute teachers and technicians. why Victorian industrial towns were so medicine, culture and history of pain. the Sciart theme, as were four Production competition is planned for 2005. of Contemporary Arts (ICA) in London. unhealthy; the second, held in June 2004, Awards of around £100 000: The Fluent Life Study, a research report describing explored changes in medicine, surgery An Advocacy and Training Interactive Heart, an original music and dance work Grants worth £2.5 million were made An innovative multimedia CD-ROM the views and attitudes of a range and our understanding of the human Guide was produced in 2004 for the inspired by the cardiovascular system, by the Wellcome Trust through the catalogue was produced for the of stakeholders and interested parties body over this period. Schistosomiasis Control Initiative (SCI). created by composer Sir John Tavener, £33 million Rediscover initiative. exhibition, featuring a gallery of works towards A-level biology, was published The CD-ROM was produced in heart imaging specialist Dr Philip Kilner This partnership with the Millennium from the exhibition, audio and video clips, in October 2003. The research was The Wellcome Library ran a programme collaboration with the SCI at Imperial and choreographer Wayne McGregor; Commission and the Wolfson Foundation and specially commissioned essays. The commissioned by the Wellcome Trust of 40-minute video-conference sessions College, London, which is funded by Projected Worlds, an exhibition and provided funds for science centres and CD-ROM catalogue was shortlisted for and carried out by the Centre for for schools. Topics included ‘What’s the the Bill and Melinda Gates Foundation. events season at Camden Arts Centre museums to redevelop their exhibits. the prestigious 2004 AXA Art Exhibition Education and Industry at the University Difference?’, looking at medical advances The CD-ROM delivers programme- exploring how scientific intervention Recipients of Trust funds included the Catalogue Award, run by the Art of Warwick. in the 19th and 20th centuries, and ‘What oriented advocacy messages and transforms our surroundings; How To Centre for Life in Newcastle upon Tyne, Newspaper and specialist insurer AXA Art. Was it Like?’, exploring Tudor and training materials to those responsible Live, a live performance by Bobby Baker, W5 at Odyssey, Belfast, Sensation in Two editions of LabNotes: New biology Victorian healthcare. During the sessions for implementing the programme. inspired by her experience of dialectical Dundee and the Eden Project in Cornwall and society – a publication providing children could see unique items from A French translation of a Lymphatic behavioural therapy and created with (see page 32). teachers with up-to-date information the Wellcome Library collections (such Filariasis CD-ROM was published in psychologist Professor Richard Hallam; on research findings in biomedicine and as Louis Pasteur’s notebooks from his August 2004. In the Topics in International and Tomorrow Belongs to Me, a series their wider social implications – were time as a student in Paris) via a video link. Health series of CD-ROMs, a revised published during the year. Ageing They then had the opportunity to ask edition of HIV/AIDS was launched covered the science and social questions about the material and the in November 2003.

Woodland ecology. PUBLIC ENGAGEMENT PUBLIC ENGAGEMENT 48 49 PUBLIC ENGAGEMENT The Wellcome Trust’s Public Engagement activities aim to raise awareness and understanding of biomedical science, its social and ethical implications and its historical context. of filmed interviews with scientific and Public participation The Wellcome Trust Gallery at the British implications of increased longevity, while subject. This enabled them to get first- medical professionals researching In September 2004 the Wellcome Trust Museum, funded by a £5.4 million grant Dying for change: Infectious disease hand experience of historically significant inherited genetic disorders, by artist and BBC Science launched the second to the British Museum, opened on in the developing world examined objects without needing to make a Jacqueline Donachie and geneticist Imagine photographic competition to 3 November 2003 with Living and Dying the reasons underlying the huge impact special trip. Dr Darren Monckton. encourage school groups, young people (see page 31). of infectious disease in resource- and adults to explore ‘how is science poor countries. The Wellcome Trust contributed A notable award under the Young changing us?’ Pharmakon ran from 17 October 2003 £750 000 to a project promoting open People’s theme was for a project at the to 6 February 2004 at the TwoTen Gallery Wellcome Library access to published scientific papers. University of Bristol, which will create The Wellcome Trust organised a series on Euston Road. The exhibition featured Significant progress was made on the Run by the Wellcome Library, the Joint young people’s Research Ethics of online debates and public events works from the US artist Beverly Fishman. cataloguing of the Wellcome Foundation Information Systems Committee and Committees. School students will with Spiked, an online publisher and Ltd archive (which was transferred to the the US National Library of Medicine, consider real grant applications and discussion forum (www.spiked- Wonderful: Visions of the near future, Wellcome Library from GlaxoSmithKline the new project will digitise the full text feed back comments to the actual online.com). The opening debate in the a major collaborative science and art in 2001). The cataloguing project will help of every issue of a number of important panels considering the applications. series, ‘Fearing the Unknown: Are we venture exploring the languages and illuminate both the early development medical journals. too risk averse?’ questioned whether assumptions of art and science and what of the Wellcome pharmaceutical Grants A total of 31 People Awards – a fast- society was excessively preoccupied happens when these research interests company and the wider history of the Publications A total of 41 Society Awards were response mechanism to support smaller with exaggerated risks. The second fuse, opened at the Arnolfini Gallery in pharmaceutical industry in the UK. Talking Heads: Cognitive behavioural awarded under the £3 million Engaging projects – were also funded under the debate, ‘Human Body Parts’, focused Bristol in February 2004. Supported by therapy comes of age, the latest Science grants programme. These large Engaging Science programme. on issues around the Human Tissue Bill, the Wellcome Trust and other partners, Public outreach, particularly with Wellcome News Supplement, was awards of £50 000 or more support including consent and the use of human Wonderful comprises a national touring schools and young people, was a feature published in June 2004. It featured public engagement projects in designated In 2003, 27 awards were made through tissue and organs in research. Debates exhibition, new commissions, live work, of the Wellcome Library’s year. Fourteen articles exploring the latest thinking areas – in 2003/04, ‘broadening access’, the Pulse initiative, which encouraged were also organised with the Institute an education CD-ROM, conference, students from South Camden Community on cognitive behavioural therapy – ‘young people’s education’ and ‘Sciart’. youth theatre and dance companies to of Contemporary Arts. The first publication and interpretative film. School, all refugees, embarked on the and how it is being applied to a wide develop new performance arts projects debate looked at privacy and questions Remedies and Recipes project. After range of disorders, including depression, Society Awards under the ‘broadening to engage young people with science. of how personal biomedical data Education visiting the Wellcome Library to examine social phobia, post-traumatic stress access’ theme included an award to The projects embraced a huge spectrum are used; the second at the pathway Construction work began on the new a range of recipe books they compiled disorder, schizophrenia and borderline Dr Guto Roberts to introduce biomedical of themes, including the bioscience from research to the media. National Science Learning Centre their own books of home cures from personality disorder. science to the National Eisteddfod of of light, neuroscience, cloning, eugenics, at the University of York, part of the both the UK and their home countries. Wales, the most important annual cultural ageing and vaccination programmes. Exhibitions £51 million national network of Science An evaluation of The Human Genome festival of Wales, and one to Dr Carolyn Pain: Passion, compassion, sensibility Learning Centres being funded by the Two GCSE Medicine Through Time microsite – which provides key Stephens at the London School of This year saw many performances ran from 13 February to 20 June 2004 Wellcome Trust and the Department INSET days were run by the Wellcome information about the human genome – Hygiene and Tropical Medicine, to see based on projects funded through Pulse. at the Medicine in Context Gallery at the for Education and Skills. The national Library in partnership with the Schools indicated that the site is a valuable and whether children’s participation in In addition, a two-day conference Science Museum (see page 30). To centre, which is due to open in autumn History Project (www.tasc.ac.uk/shp) with widely used resource; it attracted epidemiological research can stimulate at the University of Manchester (25–26 accompany the exhibition, a public event, 2005, will be run by the White Rose the aim of improving teachers’ knowledge around 280 000 visitors in the year. an interest in medical science. June 2004) featured performances and The Heartache of St Valentine's Day, was Consortium. The national network aims and increasing their confidence in A microsite was also developed to enabled participants to share thoughts held at the Dana Centre on 11 February to provide enhanced professional teaching the history of medicine. The accompany the Pain exhibition, Ten Research and Development Awards about their experiences. The initiative 2004, while a series of films and debates development opportunities for science first, held in January 2004, examined providing articles on the science, of up to £15 000 were awarded under has been so successful that a second about pain were organised at the Institute teachers and technicians. why Victorian industrial towns were so medicine, culture and history of pain. the Sciart theme, as were four Production competition is planned for 2005. of Contemporary Arts (ICA) in London. unhealthy; the second, held in June 2004, Awards of around £100 000: The Fluent Life Study, a research report describing explored changes in medicine, surgery An Advocacy and Training Interactive Heart, an original music and dance work Grants worth £2.5 million were made An innovative multimedia CD-ROM the views and attitudes of a range and our understanding of the human Guide was produced in 2004 for the inspired by the cardiovascular system, by the Wellcome Trust through the catalogue was produced for the of stakeholders and interested parties body over this period. Schistosomiasis Control Initiative (SCI). created by composer Sir John Tavener, £33 million Rediscover initiative. exhibition, featuring a gallery of works towards A-level biology, was published The CD-ROM was produced in heart imaging specialist Dr Philip Kilner This partnership with the Millennium from the exhibition, audio and video clips, in October 2003. The research was The Wellcome Library ran a programme collaboration with the SCI at Imperial and choreographer Wayne McGregor; Commission and the Wolfson Foundation and specially commissioned essays. The commissioned by the Wellcome Trust of 40-minute video-conference sessions College, London, which is funded by Projected Worlds, an exhibition and provided funds for science centres and CD-ROM catalogue was shortlisted for and carried out by the Centre for for schools. Topics included ‘What’s the the Bill and Melinda Gates Foundation. events season at Camden Arts Centre museums to redevelop their exhibits. the prestigious 2004 AXA Art Exhibition Education and Industry at the University Difference?’, looking at medical advances The CD-ROM delivers programme- exploring how scientific intervention Recipients of Trust funds included the Catalogue Award, run by the Art of Warwick. in the 19th and 20th centuries, and ‘What oriented advocacy messages and transforms our surroundings; How To Centre for Life in Newcastle upon Tyne, Newspaper and specialist insurer AXA Art. Was it Like?’, exploring Tudor and training materials to those responsible Live, a live performance by Bobby Baker, W5 at Odyssey, Belfast, Sensation in Two editions of LabNotes: New biology Victorian healthcare. During the sessions for implementing the programme. inspired by her experience of dialectical Dundee and the Eden Project in Cornwall and society – a publication providing children could see unique items from A French translation of a Lymphatic behavioural therapy and created with (see page 32). teachers with up-to-date information the Wellcome Library collections (such Filariasis CD-ROM was published in psychologist Professor Richard Hallam; on research findings in biomedicine and as Louis Pasteur’s notebooks from his August 2004. In the Topics in International and Tomorrow Belongs to Me, a series their wider social implications – were time as a student in Paris) via a video link. Health series of CD-ROMs, a revised published during the year. Ageing They then had the opportunity to ask edition of HIV/AIDS was launched covered the science and social questions about the material and the in November 2003.

Woodland ecology. FUNDING COMMITTEES FUNDING COMMITTEES 50 51

The Wellcome Trust is committed to the principles of peer review. We are indebted FUNDING to the many researchers who gave up their time to sit on our advisory committees, and to the thousands of scientific referees, in the UK and overseas, who provide COMMITTEES comments on grant applications. The following pages list the membership of our advisory committees during 2003/04.

Animal Health Professor B Turner Professor C Black Professor M C Holley Professor K Hill Professor K H G Mills Professor M Tuite Professor J M Henley in the Developing University of Birmingham Medical School (to January 2004) Royal Free Hospital University of Sheffield Johns Hopkins University, USA Trinity College Dublin, Ireland (Vice-Chair) University of Kent, University of Bristol School of Medicine, London Canterbury World Committee Professor M J Whitaker Professor C G P Mathew Dr S Jejeebhoy Professor P Morgan Professor P B Jones University of Newcastle upon Tyne Professor T J Elliott* King’s College London The Population Council, India University of Wales College of Medicine Professor J J B Jack University of Cambridge Professor H R P Miller Professor J G Williams University of Southampton Professor C S Peckham Professor R Martorell Professor J H Naismith (to February 2004) Governor, Professor E Joyce (Chair) University of Edinburgh University of Dundee Professor J Franklyn Institute of Child Health, London Emory University, USA University of St Andrews Wellcome Trust Imperial College of Science, Professor R H Gilman * Member for the PhD Advisory Board only (from January 2004) University Professor D J Porteous Professor R Sauerborn Professor J R Saunders Dr V Allan Technology and Medicine, London (Vice-Chair) John Hopkins of Birmingham Western General Hospital, Heidelberg University, Germany University of Liverpool University of Manchester Professor E A Kuipers University, USA Bioarchaeology Panel Professor I Griffiths University of Edinburgh Professor G Thornicroft Professor C M R Turner Professor P R Avner Institute of Psychiatry, London Professor M Bobrow Professor M K Jones University of Glasgow Dr L Rechaussat Institute of Psychiatry, London University of Glasgow Institut Pasteur, France Professor A P Monaco Governor, Wellcome Trust (Chair) University of Cambridge Professor C Haslett INSERM, France Dr A P Waters Professor P Cullen University of Oxford Professor C R W Edwards Professor D J Ortner University of Edinburgh Dr D Shepherd History of Medicine Panel Leiden University, The Netherlands University of Bristol Professor V H Perry Governor, Wellcome Trust (Vice-Chair) Smithsonian National Professor D Kelleher University of Southampton Professor M A Jackson Professor R A Dixon University of Southampton Professor P A Conrad Museum of Natural History, USA Trinity College Dublin, Ireland Professor B G Spratt (Chair) University of Exeter International John Innes Centre, Norwich Professor D J Price University of California-Davis, USA Professor J O Thomas Professor P F Liddle Imperial College School Professor J J B Jack Biomedical Panel Professor P S Freemont University of Edinburgh Professor M C M De Jong Governor, Wellcome Trust University of Nottingham of Medicine, London Imperial College of Science, Governor, Wellcome Trust Professor A Tait Professor G P Richardson Wageningen University, The Netherlands Technology and Medicine, London Professor L C Aiello Professor P Openshaw Functional Genomics Dr J Andrews (Chair) University of Glasgow University of Sussex Dr C Heffernan University College London (to January 2004) Imperial College Development Panel Dr A J Greenfield Oxford Brookes University Professor C R W Edwards Professor M J Riddoch University of Reading Dr D G Bradley School of Medicine, London Dr R G Hill Medical Research Council Mammalian University of Birmingham (Chair) Merck Sharp & Dohme Professor V Berridge Governor, Wellcome Trust Genetics Unit, Harwell Dr M Jeggo Trinity College Dublin, Republic of Ireland Professor M J Owen UK, Harlow London School of Hygiene Professor V Crunelli Professor B Robertson CSIRO Livestock Industries, Australia Professor J E Buikstra (to October 2003) University of Wales and Tropical Medicine Professor D G Hardie University of Strathclyde College of Medicine, Cardiff Professor Sir Michael Rutter Cardiff University University of Dundee Dr R Kock University of New Mexico, USA Governor, Wellcome Trust Professor M A Crowther Professor G E Griffin Professor P J Shaw Organisation of African Professor L Regan Professor C L Mummery Dr P Halstead University of Glasgow St George’s Hospital Medical University of Sheffield Unity/Inter African Bureau Imperial College School Dr L Beeley Netherlands Institute for University of Sheffield Dr M Harrison School, London Professor A W Stitt for Animal Resources, Kenya of Medicine, London Pfizer Central Research, Sandwich Developmental Biology, Utrecht Professor M Stoneking University of Oxford Professor B H Hirst Queen’s University of Belfast Professor G Palmer Professor A J Silman Dr R Brent Professor S Neidle Max Planck Institute for Evolutionary Mr J N P B Horden University of Newcastle upon Tyne Washington State University, USA Anthropology, Germany (from January 2004) University University of California, USA School of Pharmacy, Physiology and of Manchester University of London Professor V Horejsi University of London Dr C Peacock Professor L R Cardon Dr T Tansey Academy of Sciences Pharmacology Panel FARM-Africa, London Biomedical Ethics Panel Professor P M Stewart University of Oxford Professor M S Povey (to January 2004) University University College London of the Czech Republic University College London Professor P Vallance Professor D U Pfeiffer Mr A Tomei Professor B Charlesworth of Birmingham Professor T Treasure Professor M J Humphries (Chair) University College London Royal Veterinary College, Hatfield (Chair) Nuffield Foundation, London University of Edinburgh Professor A J Rees Professor R C Trembath Guy’s Hospital, London University of Manchester University of Aberdeen Professor S H Ralston Dr M J Witty Mr E Walker-Arnott Professor J Darlington University of Leicester Professor P van der Eijk Professor O A Krishtal (Vice-Chair) University of Aberdeen Pfizer UK, Sandwich Governor, Wellcome Trust Imperial College of Science, Professor M S Robinson Professor D M Turnbull Technology and Medicine, London University of Newcastle Bogomoletz Institute University of Cambridge Professor Dame Jean Thomas Dr C Barton of Physiology, Ukraine Basic Science (from January 2004) University Dr P Grindrod Dr J-P Vincent Governor, Wellcome Trust Papworth Hospital, Cambridge Infection and Professor R M Maizels Interest Group of Newcastle Numbercraft Ltd, Oxford National Institute for Medical Professor D Beech Professor A V Campbell Immunity Panel University of Edinburgh Professor H Watkins Dr P Jeffreys Research, London University of Leeds Professor J N P Rawlins University of Bristol Professor M McCarthy (to October 2003) University of Oxford University of Oxford Professor N A R Gow Professor J P Waltho Professor R Dimaline (Chair) University of Oxford Dr D Coles Professor A P Weetman (Chair) University of Aberdeen Oxford Centre for Diabetes, Endocrinoloy University of Sheffield University of Liverpool Professor A P Bird European Commission, Brussels Professor 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Public Engagement Rediscover Joint Professor A McFarlane Strategic Advisory Group Funders’ Committee University of Bristol Dr A Moore Ms C Matterson Professor M Bobrow European Molecular (Chair) Wellcome Trust Governor, Wellcome Trust Biology Organisation Mr E Walker-Arnott Ms C Matterson Society Awards Panel Governor, Wellcome Trust Wellcome Trust (Sciart production awards) Dr D Bell Mr E Walker-Arnott Association for Science Education Governor, Wellcome Trust Dr M Greenhough Mr P Dodd Dr H Couper (Chair) University of Cardiff Institute of Contemporary Art, London The Millennium Commission Ms M Ellis Ms C Fox Mr M D’Ancona Film London Institute of Ideas, London The Millennium Commission Ms M Fleming Professor A Irwin Ms J Donovan Artist and Writer Brunel University The Millennium Commission Dr L Goodman Professor M Jackson Mr M O’Connor Central St Martins College of Art and Design, London University of Exeter The Millennium Commission Acknowledgements The Wellcome Trust Annual Review All images are courtesy of the p. 37 synchrotron (JacobsGIBB Ms K R Huffman Dr R Persaud Sir Eric Ash We are grateful to everyone who is distributed via a mailing list held Wellcome Library, except as follows: Ltd/Crispin Wride Architectural Cornerhouse, Manchester Maudsley Hospital, London Trustee, The Wolfson Foundation agreed to be reviewed in this issue, by the Wellcome Trust. 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